A toxaphene-degrading bacterium related to Enterobacter cloacae, strain D1 isolated from aged contaminated soil in Nicaragua.
Enterobacter sp. strain D1 is a facultative anaerobic, Gram-negative heterotrophic bacterium isolated from toxaphene-contaminated soil. This organism was identified and characterized through phylogenetic and taxonomic studies. Based on 16S rDNA analysis, the strain D1 was clustered closely with the species Enterobacter cloacae subsp. dissolvens (LMG 2683) and E. cloacae (ATCC 13047T). Strain D1 resembled these E. cloacae strains with respect to various biochemical and nutritional characteristics, but also exhibited differences. Moreover, strain D1 is able to grow and survive with toxaphene supplied in the medium in the range 3-96 mg/L. Amongst the chemical components of toxaphene, octachlorocamphenes, nonachlorobornanes and decachlorobornanes were seen to be rapidly metabolized, although levels of hexachlorocamphenes and heptachlorobornanes were found to be slowly degraded, and subsequently accumulated during the last stage of the cultivation.


Clinical alarms: improving efficiency and effectiveness.
The clinical environment contains a plethora of bells, beeps, and buzzers. As clinicians, each audible disruption in the care environment must be analyzed to decide if the sound or visual is clinically significant. Alarms may signal a clinically significant change in a patient's condition (true positive), an alarm violation that is clinically insignificant (false positive), or a reflection of poorly set monitoring parameters. Our challenge is to develop monitors that are sensitive and specific. This coupled with protocols that are designed for a specific population, and customized for each individual patient, enable the caregiver to maximize the use of monitoring systems and ensure patient safety. This article guides the critical care nurse through an assessment of alarms in the critical care environment, beyond the cardiorespiratory alarms, assessing the impact of clinical and environmental alarms.


Identification of a sex-specific SCAR marker in dioecious Pandanus fascicularis L. (Pandanaceae).
Pandanus fascicularis L. is a dioecious plant native to South Asia with significant numbers in coastal areas. With the aim of distinguishing male genotypes from female genotypes early in the vegetative growth phase, the current study was initiated using molecular markers. Based on the principle of bulked segregant analysis, the sampled plants were separated into 2 bulks depending on their sex. Of the 89 random amplified polymorphic DNA and inter-simple sequence repeat markers used, one decamer (OPO-08) consistently amplified a 1263 bp band in the males that was absent in the females. Its DNA sequence did not exhibit significant similarity to previously characterized sequences, but the presence of mononucleotide and dinucleotide repeats suggested that it was a repeat-rich region. A sequence-characterized amplified region marker (MSSRF-01) designed for this fragment continued to amplify the specific allele in all the male plants. Southern hybridization performed using the sex-specific fragment as a probe yielded results consistent with those previously obtained by polymerase chain reaction. These results strongly suggest that MSSRF-01 is a male-specific molecular marker. With no information available on the presence of sex chromosomes in Pandanus, this marker can be used to differentiate the sexes.


Effects of sucrose and copigment sources on the major anthocyanins isolated from sour cherries.
Cyanidin-3-O-glucosylrutinoside and cyanidin-3-O-rutinoside were isolated from sour cherry juice concentrate (SCJC). Sucrose and copigments [gallic acid (GA), cherry stem extract (CSE) and pomegranate rind extract (PRE)] were added to these anthocyanins. Effects of sucrose and copigments on the isolated anthocyanins were studied during storage at 20 °C for 140 days. All copigment sources provided protection against degradation effect of sucrose on the isolated anthocyanins before storage. Although GA increased the stabilities of both isolated anthocyanins, only CSE had copigmentation effect on both isolated anthocyanins. Copigmentation effect on cyanidin-3-O-glucosylrutinoside continued throughout storage. However, this effect on cyanidin-3-O-rutinoside continued for only 56 days of storage. Cyanidin-3-O-glucosylrutinoside containing three sugar moieties was more prone to copigmentation than cyanidine-3-rutinoside containing two sugar moieties. Results showed that the presence of more than one anthocyanin in a media changed stability of copigmentation. We recommend CSE for enhancement in colour density, but GA for enhancement in anthocyanin stability.


Prevalence and Risk Factors of Avian Chlamydiosis Detected by Polymerase Chain Reaction in Psittacine Birds in Thailand.
This study surveyed avian chlamydiosis, with the aim to estimate the prevalence and potential risk factors associated with Chlamydia psittaci infection in psittacine birds kept as domestic pets in Thailand. Oropharyngeal swabs were collected from 120 psittacine birds that were randomly selected from hospitals in the central (Bangkok) and northeastern regions (Khon Kaen) of Thailand between 2019 and 2021. The oropharyngeal swabs were subject to polymerase chain reaction testing to detect the C psittaci ompA gene. The prevalence of C psittaci was 2.5% (3/ 120, 95% confidence interval = 0.3-5.3). Of the 3 positive birds, 1 was a Forpus parrot (Forpus species)(CP43TH) and 1 was an African grey parrot (Psittacus erithacus)(CP49TH) from Bangkok; both were juvenile birds with clinical signs of disease. The third positive bird (CP12TH) was a subclinical adult sun conure (Aratinga solstitialis) from Khon Kaen. Two sequences of samples that were previously identified in human psittacosis cases (accession numbers MK032053.1 and HM450409.1) were also examined. Since there was a low number of infected birds, potential associations between C psittaci infection and various environmental variables (eg, cage cleaning, synanthropic birds, quarantine of new birds, and overcrowding) were assessed by Fisher exact tests. This study provides estimates of the prevalence and potential risk factors associated with C psittaci infection in psittacine birds from central (Bangkok) and the northeastern regions (Khon Kaen) of Thailand. The detection of C psittaci in captive psittacine birds demonstrates that there is a possibility for bird-to-bird transmission as well as some zoonotic potential for the human caretakers of these birds. Furthermore, larger-scale studies should be conducted to confirm these findings.


How well can the Caco-2/Madin-Darby canine kidney models predict effective human jejunal permeability?
The study aimed to predict effective human jejunal permeability (P(eff)) using a biophysical model based on parametrized paracellular, aqueous boundary layer, and transcellular permeabilities, and the villus-fold surface area expansion factor (k(VF)). Published human jejunal data (119 P(eff), 53 compounds) were analyzed by a regression procedure incorporating a dual-pore size paracellular model. Transcellular permeability, scaled by k(VF), was equated to that of Caco-2 at pH 6.5. The biophysical model predicted human jejunal permeability data within the experimental uncertainty. This investigation revealed several surprising predictions: (i) many molecules permeate predominantly (but not exclusively) by the paracellular route, (ii) the aqueous boundary layer thickness in the intestinal perfusion experiments is larger than expected, (iii) the mucosal surface area in awake humans is apparently nearly entirely accessible to drug absorption, and (iv) the relative "leakiness" of the human jejunum is not so different from that observed in a number of published Caco-2 studies.


Intensive Care of Pulmonary Complications Following Liver Transplantation.
Chronic liver disease has been associated with pulmonary dysfunction both before and after liver transplantation. Post-liver transplantation pulmonary complications can affect both morbidity and mortality often necessitating intensive care during the immediate postoperative period. The major pulmonary complications include pneumonia, pleural effusions, pulmonary edema, and atelectasis. Poor clinical outcomes have been known to be associated with age, severity of liver dysfunction, and preexisting lung disease as well as perioperative events related to fluid balance, particularly transfusion and fluid volumes. Delineating each and every one of these pulmonary complications and their associated risk factors becomes paramount in guiding specific therapeutic strategies.


COVID-19 prevention behaviors, trust, and intent to vaccinate among youth at risk for HIV.
The current study examines COVID-19 prevention behaviors and vaccine intentions among 83 youth at high risk for HIV. Most youth self-identified as Latinx (52%), cisgender men (84%), and homosexual (66%). Youth self-reported COVID-19 prevention behaviors and intentions to vaccinate. Participants reported wearing face masks, washing hands, and staying six feet apart, but fewer reported leaving home only for essential needs. About one-third reported that they would not get a vaccine, and lack of trust in their doctors and the government were significantly associated with non-intention. To improve efforts towards herd immunity, interventions to improve health messaging from trusted sources for at-risk youth may be necessary to achieve higher vaccine uptake.


Making products available among community health workers: Evidence for improving community health supply chains from Ethiopia, Malawi, and Rwanda.
A UNICEF review of the challenges to scaling up integrated community case management (iCCM) found that drug shortages were a common bottleneck. In many settings, little thought has gone into the design of supply chains to the community level and limited evidence exists for how to address these unique challenges. SC4CCM's purpose was to conduct intervention research to identify proven, simple, affordable solutions that address the unique supply chain challenges faced by CHWs and to demonstrate that supply chain constraints at the community level can be overcome. SC4CCM selected three countries to implement supply chain innovations and developed a theory of change (TOC) framework for the learning phase, which identified the main drivers of product availability and was used for baseline assessments, design, implementation and evaluation of interventions in Ethiopia, Malawi, and Rwanda. Interventions were developed in each country and tested over 12-24 months. Mixed-method follow up assessments were conducted in each country in 2012-2013. The Supply Chain for Community Case Management (SC4CCM) Project then simplified the TOC into a Community Health Supply Chain (CHSC) framework to enable cross country analysis. The findings from interventions in the three countries suggest that the greatest supply chain benefits are realized when all three CHSC framework elements (data flow, product flow, and effective people) are in place and working together. The synergistic effect of these three elements on supply chain performance was most effectively demonstrated by results from the Enhanced Management and Quality Collaborative interventions in Malawi and Rwanda, respectively, which were characterized by lower mean stockout rates and higher in stock rates on day of visit, when compared to other interventions. Many conditions are necessary to ensure continuous product availability at the community level, however a supply chain works best when three key elements (product flow, data flow, and effective people) are deliberately included as an integral part of the system design. Although these elements may be designed differently in different settings, streamlining and synchronizing them while ensuring inclusion of all components for each element improves supply chain performance and promotes product availability at the community level.


Gene control by phosphoproteins: a theoretical model for eukaryotic DNA regulation.
Although gene regulatory mechanisms in eukaryotic cells are complex, some progress is being made in understanding them. Chromosomal proteins may play a significant role in genome function and gene control. More specifically, a central role may be played by the nuclear nonhistone proteins. It appears that both viral transformation and steroid hormone action may be associated with the phosphorylation of these proteins. Recent studies have revealed that some oncogenic viruses are capable of producing viral transforming proteins with protein kinase activity. This suggests how they may subvert normal gene regulatory mechanisms. Furthermore, the effects of the steroid-receptor complex on nuclear nonhistone proteins may be similar to the effects of these viral transforming proteins, but in a controlled sense. A model of gene-regulatory, nuclear phosphorylation reactions is formulated which suggests how some oncogenic viruses may control normal gene regulatory mechanisms and how steroid hormones may interact with these same mechanisms. Such a model may reveal how disruption of these same mechanisms leads to carcinogenesis.


Combined effect of cerebral hypoperfusion and white matter lesions on executive functioning - The SMART-MR study.
It has been hypothesized that cerebral hypoperfusion may contribute to cognitive deterioration. Patients with white matter lesions (WML) may be more vulnerable to a decrease in cerebral blood flow (CBF) due to an impaired autoregulation. We investigated the association between CBF and cognitive performance and whether WML modified this relation. Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 472 patients (mean age 57 +/- 10 years, 77% male). Total CBF was measured with magnetic resonance angiography in the internal carotid arteries and basilar artery, and was expressed per 100 ml brain volume. Neuropsychological tests assessing executive functioning and memory were performed and composite scores were calculated. We used linear regression analyses, adjusted for age, sex, education and intelligence, to investigate the association between CBF and cognitive performance. We found that WML modified the association between CBF and executive functioning (p for interaction <0.001); the association between lower CBF and worse performance on executive functioning became stronger and significant with increasing volumes of WML. Lower CBF was not associated with worse memory. Our results suggest that a combination of lower CBF and WML may impair executive functioning but not memory.


Discontinuous native protein gel electrophoresis.
Analysis of the oligomeric state of a native protein usually requires analytical ultracentrifugation or repeated gel filtration to calculate the protein's size. We have developed a discontinuous native protein gel electrophoresis system that allows the separation of even basic proteins according to their size, oligomeric state, and shape. This gel system combines the addition of negative charges to the proteins by Serva Blue G with a discontinuous buffer system and gradient gels. As in SDS-PAGE, chloride constitutes the high mobility anion in the gel and anode buffer. However, for sample focusing this system employs histidine instead of glycine as the slow dipolar ion following from the cathode buffer to improve migration of basic proteins. In addition, proteins run into gel pores corresponding to their size and shape in the gradient gel. Using this gel system, we show that the polypyrimidine tract-binding protein (PTB) is a monomer.


[A correlation study between diarrhea-predominant irritable bowel syndrome complicated functional dyspepsia patients of Gan-stagnation Pi-deficiency syndrome and gastrointestinal hormones].
To investigate the correlation between the pathogeneses of diarrhea-pre- dominant irritable bowel syndrome (D-IBS) complicated functional dyspepsia (FD) patients of Gan-stagnation Pi-deficiency Syndrome (GSPDS) and symptoms, psychological states, and gastrointestinal hormones. A total of 111 patients with confirmed D-IBS complicated FD of GSPDS were recruited as the treated group by using Rome III standard and Chinese medical syndrome standard. And 30 healthy volunteers were recruited as the control group. The general condition, scoring for digestive symptoms, and the distribution of GSPDS subtype of all subjects were recorded by a questionnaire, and assessed by Symptom Checklist (SCL-90; a software for psychological test developed by Beijing Huicheng Adult Cor- poration). Meanwhile, plasma levels of 5-hydroxytryptamine (5-HT), somatostatin (SS), vasoactive intestinal peptide (VIP), endothelin (ET), interleukin 10 (IL-10), and interleukin 12 (IL-12) were measured in all subjects. (1) The subtype of D-IBS complicated FD of GSPDS was dominant in Pi-qi deficiency type (51/111,45.9%),Pi yang deficiency type (34/111,30.6%), and GSPDS. There was no statistical difference in the scoring of digestive symptoms among the 3 subtypes (P >0.05). (2) Compared with the control group, the anxiety factor score and the total score significantly increased in all three subtypes of D-IBS complicated FD of GSPDS, and the depression score of Pi yang deficiency type and Gan-depression type also significantly increased (P <0.05, P <0.01); the depression score of Gan-depression type was significantly higher than that of the Pi-qi deficiency type (P <0.01). Plasma 5-HT levels were obviously lower in D-IBS complicated FD patients of GSPDS accompanied with anxiety or depression than in those with no obvious psychological abnormalities, and VIP and IL-10 levels were significantly lower than those in the control group (P <0.05). Plasma VIP levels were also obviously lower in D-IBS complicated FD patients of GSPDS accompanied with anxiety or depression than in those with no obvious psychological abnormalities (P <0.01), and SS levels were significantly lower than those in the control group (P <0.05). There was no statistical difference in plasma ET or IL-12 levels in each patient group, when compared with the control group (P >0.05). (3) Compared with the.control group, plasma 5-HT levels significantly increased, plasma VIP and IL-10 levels significantly decreased in ach subtype of D-IBS complicated FD patients of GSPDS (P <0.05, P <0.01), and no significant change of SS, ET, or IL-12 occurred (P >0.05). Besides, plasma 5-HT levels were significantly higher in Gan-depression type than in Pi yang deficiency type, VIP levels were lower in Gan-depression type than in Pi-qi deficiency type (all P <0.05). Gan stagnation and Pi deficiency were dominant in D-IBS complicated FD patients of GSPDS. Psychological abnormalities, increased plasma 5-HT levels, and decreased plasma VIP levels were closely correlated with Gan stagnation subtype, which provided some reference for looking for objective indicators of Chinese medical syndromes in treating D-IBS complicated FD patients of GSPDS.


Intrapartum intervention rates and perinatal outcomes following induction of labour compared to expectant management at term from an Australian perinatal centre.
Induction of labor (IOL) is a common obstetric intervention, yet its impact on intervention rates and perinatal outcomes is conflicting. To evaluate the impact of IOL on intrapartum intervention rates and perinatal outcomes in women with singleton pregnancies at term. This was a retrospective, cross-sectional study of term singleton deliveries at the Mater Mother's Hospital in Brisbane, Australia in 2007-2013. The IOL cohort was compared to an expectantly managed group. Of the final cohort (44 698 women), 64.4% had expectant management and 35.6% had IOL. Multivariate analyses showed that IOL was associated with lower odds of spontaneous vaginal delivery from ≥37 weeks gestation. The risk of emergency caesarean for non-reassuring fetal status was also higher in the IOL cohort at 40 and 41 weeks gestation. For women who were managed expectantly, the highest rate of spontaneous vaginal delivery and the lowest rate of emergency caesareans occurred at 39 weeks gestation. For women who underwent IOL, the nadir emergency caesarean rate and the highest spontaneous vaginal delivery rate was also at 39 weeks. Rates of neonatal intensive car unit admission were higher in the IOL group at 37 weeks (adjusted odds ratio (aOR) 3.11, 95% CI: 2.62-3.68) and 38 weeks (aOR 1.78, 95% CI: 1.55-2.04) and lower at >42 weeks (OR 0.35, 95% CI: 0.14-0.81) respectively. IOL compared to expectant management is associated with lower spontaneous vaginal delivery rates and increased risk of emergency caesarean for intrapartum fetal compromise with broadly comparable perinatal outcomes.


A case of tumor of the follicular infundibulum with sebaceous differentiation.
Tumor of the follicular infundibulum (TFI) is an uncommon benign adnexal tumor that usually presents as a solitary keratotic papule on the face or scalp of elderly patients. Histopathologically, it typically manifests as a plate-like fenestrated proliferation of monomorphic pale-staining cells. A 76-year-old male presented with about a 2 cm, well-defined, yellowish to brownish, slightly elevated, twisted and bent, interrupted, cord-like plaque on his left lower abdomen. Microscopic examination revealed a sharply demarcated plate-like proliferation of pale cells localized in the papillary dermis with multiple connections to the overlying epidermis. The histopathological features were compatible with TFI, except for foci of sebaceous differentiation. There has been one previous case report of TFI with sebaceous differentiation in the English medical literature. Herein, we report on a singular case of TFI with sebaceous differentiation.


Ginsenoside Rb2 inhibits epithelial-mesenchymal transition of colorectal cancer cells by suppressing TGF-β/Smad signaling.
Treating colorectal cancer (CRC) continues to be a clinical challenge. Studies have shown that epithelial-mesenchymal transition (EMT) is a critical step in tumor progression and transforming growth factor-β1 (TGF-β1) signaling has been shown to play a crucial role in EMT. Here, we investigate the inhibition effect of Ginsenoside Rb2, main bioactive component of ginseng, in human colorectal cancer cells via TGF-β1. The current study aims to study the inhibitory effect of Ginsenoside Rb2 on HCT116 and SW620 cells and its anti-tumor mechanism. Histomorphological analysis and western blot analysis were performed to evaluate expression of TGF-β1 in human cancerous colon samples and the adjacent normal samples. The docking simulation assay were performed to explore the potential mode of binding of Ginsenoside Rb2 to the TGF-β1 protein. CCK8, adhesion and invasion assay were used to assess the effects of Ginsenoside Rb2 in HCT116 and SW620 cells. RT-PCR, Western blot and Immunohistochemical staining were employed to detect the TGF-β1-related signaling pathways in the colon cancer cells and/or xenograft mice. The expression of TGF-β1 in human cancerous colon samples was significantly increased compared with the adjacent normal samples. Ginsenoside Rb2 inhibit the growth, adhesion, EMT and metastasis of human colorectal cancer cells. The docking simulation assay confirmed that Ginsenoside Rb2 bound to the hydrophobic pocket of TGF-β1, which partially overlaps with the binding sites on TGF-β1, and thus disrupted TGF-β1 dimerization. Western Blot analysis further confirmed that Ginsenoside Rb2 could inhibit the expression of TGF-β1 in vitro and in vivo. Furthermore, Ginsenoside Rb2 could inhibit the expression of Smad4 and phosphorylated Smad2/3. Ginsenoside Rb2 could inhibit EMT of colorectal cancer cells through the TGF-β1/Smad signaling, and might be a potential candidate for the treatment of colorectal cancer.


Unforeseen Complications: A Case of Subdural Anesthesia Post-epidural Insertion.
Subdural anesthesia, although rare, is a significant complication of epidural anesthesia. This case report presents a 28-year-old female patient who developed sudden unconsciousness following epidural anesthesia administration for labor pain. Despite no evident contraindications to epidural anesthesia, she lost consciousness shortly after the initial test dose, leading to an emergency cesarean section under general anesthesia. The neonate showed signs of fetal bradycardia post-epidural and required intensive care. The patient made a complete recovery with no postpartum complications. This report underlines the need for vigilant monitoring and the importance of swift interventions in case of complications arising from epidural anesthesia.


Application of Box-Behnken experimental design to optimize the extraction of insecticidal Cry1Ac from soil.
A validated method for analyzing Cry proteins is a premise to study the fate and ecological effects of contaminants associated with genetically engineered Bacillus thuringiensis crops. The current study has optimized the extraction method to analyze Cry1Ac protein in soil using a response surface methodology with a three-level-three-factor Box-Behnken experimental design (BBD). The optimum extraction conditions were at 21 °C and 630 rpm for 2 h. Regression analysis showed a good fit of the experimental data to the second-order polynomial model with a coefficient of determination of 0.96. The method was sensitive and precise with a method detection limit of 0.8 ng/g dry weight and relative standard deviations at 7.3%. Finally, the established method was applied for analyzing Cry1Ac protein residues in field-collected soil samples. Trace amounts of Cry1Ac protein were detected in the soils where transgenic crops have been planted for 8 and 12 years.


Prospects for engineering and improvement of cross-protective virus strains.
Mild strain cross-protection is currently an important method for the production of high quality plant products; despite challenge from severe virus isolates the initial protecting strain precludes symptom development. The mechanism of cross-protection is not yet resolved as RNA silencing does not sufficiently explain the phenomenon. Six requirements have been put forward to ensure long-lasting protection. We propose two additional requirements for effective and durable mild strain cross-protection; mild strains based on knowledge of the mechanism and consideration of impacts to consumers. Future research on predicting phenotype from genotype and understanding virus-plant and virus-vector interactions will enable improvement of cross-protective strains. Shared international databases of whole ecosystem interactions across a wide range of virus patho- and symbiotic-systems will form the basis for making step-change advances towards our collective ability to engineer and improve mild strain cross-protection.


Epidemiology of symptomatic ossification of the posterior longitudinal ligament: a nationwide registry survey.
Ossification of the posterior longitudinal ligament (OPLL) is radiographically detectable in 3-6% of Asian individuals, although not all detectable OPLL cases lead to myelopathy. To date, it is unknown how many patients suffer from neurological symptoms due to OPLL. The purpose of this study was to investigate the epidemiology of symptomatic OPLL using Japan's national registry database. We examined the registry data of patients with OPLL who held a certificate of medical subsidy from the Japanese Ministry of Health, Labor and Welfare. The study period was from January 1, 2011 to December 31, 2012. Registry data revealed that the incidence and the period prevalence of symptomatic OPLL were 0.005% (5 per 100,000 population) and 0.027% (27 per 100,000 population), respectively. OPLL occurred twice as often in men as in women. The peak age for onset of symptoms was 60-69 years. The mean Japanese Orthopedic Association (JOA) score was 9 points. Ninety percent of OPLL patients underwent surgery, and 90% of these surgeries were performed with a posterior approach. The most common indication for surgery was a JOA score of 11 points. According to registry data, the prevalence of symptomatic OPLL was less than one-hundredth of that of radiographically detected OPLL. This indicates that most cases of radiographically detectable OPLL may be asymptomatic.


Standardized Approach to Quantitatively Measure Residual Limb Skin Health in Individuals with Lower Limb Amputation.
Objective: (1) Develop a standardized approach to quantitatively measure residual limb skin health. (2) Report reference residual limb skin health values in people with transtibial and transfemoral amputation. Approach: Residual limb health outcomes in individuals with transtibial (n = 5) and transfemoral (n = 5) amputation were compared to able-limb controls (n = 4) using noninvasive imaging (hyperspectral imaging and laser speckle flowmetry) and probe-based approaches (laser doppler flowmetry, transcutaneous oxygen, transepidermal water loss, surface electrical capacitance). Results: A standardized methodology that employs noninvasive imaging and probe-based approaches to measure residual limb skin health are described. Compared to able-limb controls, individuals with transtibial and transfemoral amputation have significantly lower transcutaneous oxygen tension, higher transepidermal water loss, and higher surface electrical capacitance in the residual limb. Innovation: Residual limb health as a critical component of prosthesis rehabilitation for individuals with lower limb amputation is understudied in part due to a lack of clinical measures. Here, we present a standardized approach to measure residual limb health in people with transtibial and transfemoral amputation. Conclusion: Technology advances in noninvasive imaging and probe-based measures are leveraged to develop a standardized approach to quantitatively measure residual limb health in individuals with lower limb loss. Compared to able-limb controls, resting residual limb physiology in people that have had transfemoral or transtibial amputation is characterized by lower transcutaneous oxygen tension and poorer skin barrier function.


Tn1 insertion in Col Ib plasmid.
Eight clones ColIb::Tn1 were isolated by means of transformation of E. coli 921 with DNA ColIb, RP4. Linkage between markers controlling ampicillin-resistance and synthesis of colicine was found in conjugation and transduction experiments.


Influence of in vivo copper on MR images of the liver in rats.
To investigate the effects of in vivo copper on magnetic resonance (MR) images, the authors studied Long-Evans cinnamon rats, which develop hepatitis and hepatocellular carcinoma as a result of abnormal copper metabolism. The livers of the rats were imaged before hepatitis developed; the absence of hepatic disease was confirmed histopathologically. The copper that accumulated in the liver of the rats was thought to exist in the form of divalent ions, which were suspected of reducing the T1 and T2 of neighboring protons. However, the signal intensities of the liver on T1- and T2*-weighted images did not change, suggesting that in vivo copper, even when accumulated abnormally, does not influence the signal intensity of MR images.


Regulation of autolysins in teichuronic acid-containing Bacillus subtilis cells.
Bacillus subtilis cells grown under phosphate starvation induce teichuronic acid (TUA) synthesis while simultaneously repressing teichoic acid synthesis (TA). The turnover rates of TA-containing and TUA-containing walls are similar, indicating that autolysin function is similar and suggesting that modulation of autolytic function may be similar. In this study, it is demonstrated, utilizing fluorescein isothiocyanate (FITC)-dextran to probe the wall pH, that a low pH exists in the wall matrix. A second probe, cationized ferritin (CF), was used to observe cell surface protonation. Suspensions of B. subtilis cells containing either TA or TUA were aggregated with CF only after the addition of a proton-motive-force-dissipating agent. Respiring B. subtilis TUA-containing cells labelled with FITC-dextran exhibited little fluorescence. Conversely, fluorescence intensities exhibited by cells de-energized with nitrogen gas were significantly greater. The effects of protonmotive force on autolytic activity were studied by adding cell wall protein extract containing concentrated autolysin to exponentially growing TA-containing and TUA-containing B. subtilis cells. Both TUA-containing and TA-containing cells were lysed only after the addition of sodium azide. These data suggest that during normal growth the wall of TUA-containing B. subtilis cells is protonated, and proton-motive force influences autolytic regulation in both TUA-containing and TA-containing B. subtilis cells.


Bioindicator production with Bacillus atrophaeus' thermal-resistant spores cultivated by solid-state fermentation.
Bacillus atrophaeus' spores are used in the preparation of bioindicators to monitor the dry heat, ethylene oxide, and plasma sterilization processes and in tests to assess sterilizing products. Earlier production methods involved culture in chemically defined medium to support sporulation with the disadvantage of requiring an extended period of time (14 days) besides high cost of substrates. The effect of cultivation conditions by solid-state fermentation (SSF) was investigated aiming at improving the cost-productivity relation. Initial SSF parameters such as the type of substrate were tested. Process optimization was carried out using factorial experimental designs and response surface methodology in which the influence of different variables--particle size, moisture content, incubation time, pH, inoculum size, calcium sources, and medium composition--was studied. The results have suggested that soybean molasses and sugarcane bagasse are potential substrate and support, respectively, contributing to a 5-day reduction in incubation time. Variables which presented significant effects and optimum values were mean particle size (1.0 mm), moisture content (93%), initial substrate pH (8.0), and water as a solution base. The high-yield spore production was about 3 logs higher than the control and no significant difference in dry heat resistance was observed.


Obesity and health risks.
Childhood obesity is multi-factorial in etiology. Several factors contribute to the etiology of childhood obesity, and childhood obesity is itself associated with significant morbidity. This article focuses on the health risks of childhood obesity and on the prenatal and childhood influences that contribute to the genesis of childhood obesity.


Evidence of abnormal dopaminergic control of prolactin in patients with hypothalamic and pituitary tumors.
Prolactin secretion was investigated in an attempt to identify the patterns of responses in different types of tumors. Forty four patients were studied: thirty patients with prolactinomas (Group 2); nine patients with growth-hormone (GH)-adrenocorticotropic hormone (ACTH)-secreting pituitary tumors and hypothalamic tumors (Group 3); and five patients with non-secreting pituitary tumors (Group 4). A control group (Group 1) consisted of 60 healthy subjects (30 males and 30 females). All were submitted to testing by nomifensine (Nom), domperidone (Dom) and thyrotropin releasing hormone (TRH). The prolactin levels were measured by radioimmunoassay (RIA). In group 2 the suppression of PRL with Nom and the stimulation with Dom and TRH were significantly lower than in the control group (p less than 0.001). There was no statistically significant difference between groups 2 and 3 in the suppression with Nom. The increase with Dom in group 3 was significantly greater than that in group 2 (p less than 0.001) and less than that in the control group (p less than 0.005). The rise in PRL with TRH was also significantly higher in group 3 than in group 2 (p less than 0.001) and similar to that of the control group. Group 4 gave the same results as the control group to all 3 tests. Our results indicate a dopaminergic irregularity in the hypothalamic and GH-ACTH-secreting pituitary tumors, thus supporting a hypothalamic etiopathogenesis of these tumors. The normality of the GH-ACTH-secreting pituitary tumors and hypothalamic tumor responses to TRH is one more factor in differentiating these from prolactinomas. The normal response of the non-secreting tumors may involve a primary pituitary etiology of these tumors.


Serotype distribution, antimicrobial susceptibility and molecular epidemiology of invasive Streptococcus pneumoniae in the nine-year period in Serbia.
Streptococcus pneumoniae is one of the leading bacterial pathogens that can cause severe invasive diseases. The aim of the study was to characterize invasive isolates of S. pneumoniae obtained during the nine-year period in Serbia before the introduction of the pneumococcal conjugate vaccines (PCVs) into routine vaccination programs by determining: serotype distribution, the prevalence and genetic basis of antimicrobial resistance, and genetic relatedness of the circulating pneumococcal clones. A total of 490 invasive S. pneumoniae isolates were included in this study. The serotype, antimicrobial susceptibility, and ST of the strains were determined by the Quellung reaction, disk- and gradient-diffusion methods, and multilocus sequence typing (MLST), respectively. The most common serotypes in this study were 3, 19F, 14, 6B, 6A, 19A, and 23F. The serotype coverages of PCV10 and PCV13 in children less than 2 years were 71.3 and 86.1%, respectively, while PPV23 coverage in adults was in the range of 85-96%, depending on the age group. Penicillin and ceftriaxone-non-susceptible isolates account for 47.6 and 16.5% of all isolates, respectively. Macrolide non-susceptibility was detected in 40.4% of isolates, while the rate of multidrug- and extensive-drug resistance was 20.0 and 16.9%, respectively. The MLST analysis of 158 pneumococci identified 60 different STs belonging to the 16 Clonal Complexes (CCs) (consisting of 42 STs) and 18 singletons. The most common CC/ST were ST1377, CC320, CC15, CC273, CC156, CC473, CC81, and CC180. Results obtained in this study indicate that the pre-vaccine pneumococcal population in Serbia is characterized by high penicillin and macrolides non-susceptibility, worrisome rates of MDR and XDR, as well as a high degree of genetic diversity. These findings provide a basis for further investigation of the changes in serotypes and genotypes that can be expected after the routine introduction of PCVs.


Health promotion in the practice setting: findings from a review of clinical issues.
Many agencies over the last few decades have called for the explicit inclusion and application of health promotion in all aspects of nursing practice. This article reviews the body of empirical (research-based) and theoretical (conceptual) literature addressing health promotion in nursing clinical practice, to uncover its nature, intention, and impact. The aim of this review was to identify from the nursing literature what is reported on in relation to health promotion activity, both theoretical and clinical in the practice setting. An extensive review identified that literature pertaining to these issues clustered around the categories of: theorising and conceptualising the meaning and purpose of health promotion in nursing practice, the development and testing of tools and models for practice, and the exploration of attitudes, behaviours, roles and functions of nurses and health professionals in practice. Against more recent trends in health promotion, the literature shows that broader and wide-ranging health promotion reform has yet to have universal impact, whereas conventional health education activities remain the mainstay for the majority of "health promotion" activities in nursing practice. Where nurses purport to be conducting "health promotion" they are often conducting behavioural, lifestyle, and risk-orientated health education. The findings of this review therefore support the notion that much of nursing-related health practice is firmly located in reactive ill health and disease risk-specific preventive locations, instead of incorporating and instilling broader societal, economic, ecological, and political dimensions of health promotion. Recommendations for wider reform, developed from personal opinion and supported by the literature, are presented. It is argued that nursing bodies, as well as individual nurses themselves, should seek current health promotion locations in nursing practice, and find effective ways to implement health promotion strategies and, subsequently, equip practitioners with the necessary resources and skills to engage with other health promotion agencies. Future research should be aimed at implementing and evaluating broad health promotion processes.


Network-Based Systems Analysis Explains Sequence-Dependent Synergism of Bortezomib and Vorinostat in Multiple Myeloma.
Bortezomib and vorinostat exhibit synergistic effects in multiple myeloma (MM) cells when given in sequence, and the purpose of this study was to evaluate the molecular determinants of the interaction using a systems pharmacology approach. A Boolean network model consisting of 79 proteins and 225 connections was developed using literature information characterizing mechanisms of drug action and intracellular signal transduction. Network visualization and structural analysis were conducted, and model simulations were compared with experimental data. Critical biomarkers, such as pNFκB, p53, cellular stress, and p21, were identified using measures of network centrality and model reduction. U266 cells were then exposed to bortezomib (3 nM) and vorinostat (2 μM) as single agents or in simultaneous and sequential (bortezomib for first 24 h, followed by addition of vorinostat for another 24 h) combinations. Temporal changes for nine of the critical proteins in the reduced Boolean model were measured over 48 h, and cellular proliferation was measured over 96 h. A mechanism-based systems model was developed that captured the biological basis of a bortezomib and vorinostat sequence-dependent pharmacodynamic interaction. The model was further extended in vivo by linking in vitro parameter values and dynamics of p21, caspase-3, and pAKT biomarkers to tumor growth in xenograft mice reported in the literature. Network-based methodologies and pharmacodynamic principles were integrated successfully to evaluate bortezomib and vorinostat interactions in a mechanistic and quantitative manner. The model can be potentially applied to evaluate their combination regimens and explore in vivo dosing regimens.


MAD phasing: probabilistic estimate of [F (oa)].
The method of the joint probability distribution function is applied in order to estimate the structure-factor moduli of the anomalous scatterer substructure. The two-wavelength case is examined: the prior knowledge of the moduli [F(1)(+)], [F(1)(-)], [F(2)(+)], [F(2)(-)] is used to predict the value of [F(oa)] arising from the normal scattering of the anomalous scatterers. The conclusive formula is applied to ideal and to real cases: evidence of the usefulness of the approach is obtained.


Prevention of the Aggregation of Nanoparticles during the Synthesis of Nanogold-Containing Silica Aerogels.
Nanogold is widely used in many areas of physics and chemistry due to its environment-sensitive plasmon resonance absorption. The immobilization of gold nanoparticles in highly porous silica aerogel offers an attractive alternative to liquid gold solutions as they show a mechanically stable structure, are permeable to gases, and can even be used at elevated temperatures. We have found that the commercially available citrate-stabilized 10 nm gold nanoparticles may suffer from aggregation prior to or under the base-catalyzed gelation process of tetramethoxy silane. In the wet gels, Au particles increased in size, changed shape, and demonstrated the loss of plasmon resonance absorption, due to the formation of larger aggregates. We have studied a range of water-miscible organic solvents, stabilizing agents, and the gelation conditions to minimize changes from occurring in the aerogel setting and the supercritical drying process. It has been found that atmospheric carbon dioxide has a significant effect on aggregation, and it cannot be entirely excluded under normal synthetic conditions. Methanol resulted in an increase in the particle size only, while dimethyl sulfoxide, dimethylformamide, and urea changed the shape of nanoparticles to rod-like shapes, and diols led to an increase in both size and shape. However, using the polymeric stabilizer poly(vinyl pyrrolidone) efficiently prevented the aggregation of the particles, even in the presence of high concentrations of carbon dioxide, and allowed the production of nanoAu containing silica aerogels in a single step, without the modification of technology.


Calculations of oxide formation on low-index Cu surfaces.
Density-functional theory is used to evaluate the mechanism of copper surface oxidation. Reaction pathways of O2 dissociation on the surface and oxidation of the sub-surface are found on the Cu(100), Cu(110), and Cu(111) facets. At low oxygen coverage, all three surfaces dissociate O2 spontaneously. As oxygen accumulates on the surfaces, O2 dissociation becomes more difficult. A bottleneck to further oxidation occurs when the surfaces are saturated with oxygen. The barriers for O2 dissociation on the O-saturated Cu(100)-c(2×2)-0.5 monolayer (ML) and Cu(100) missing-row structures are 0.97 eV and 0.75 eV, respectively; significantly lower than those have been reported previously. Oxidation of Cu(110)-c(6×2), the most stable (110) surface oxide, has a barrier of 0.72 eV. As the reconstructions grow from step edges, clean Cu(110) surfaces can dissociatively adsorb oxygen until the surface Cu atoms are saturated. After slight rearrangements, these surface areas form a "1 ML" oxide structure which has not been reported in the literature. The barrier for further oxidation of this "1 ML" phase is only 0.31 eV. Finally the oxidized Cu(111) surface has a relatively low reaction energy barrier for O2 dissociation, even at high oxygen coverage, and allows for facile oxidation of the subsurface by fast O diffusion through the surface oxide. The kinetic mechanisms found provide a qualitative explanation of the observed oxidation of the low-index Cu surfaces.


Endothelin-1 receptor blockade prevented the electrophysiological dysfunction in cardiac myocytes of streptozotocin-induced diabetic rats.
Diabetes mellitus is complicated with the development of cardiac contractile dysfunction and electrical instability, which contributes to high morbidity and mortality in diabetic patients. This study examined the possible roles of enhanced endothelin-1 (ET-1) on diabetes-induced alterations in ventricular myocyte electrophysiology. Type 1 diabetic rats were induced by single dose injection of streptozotocin (STZ) and treated with or without ET-1 receptor antagonist bosentan for 8 wk before myocyte isolation. Action potential, outward K+ currents, and inward Ca2+ currents in ventricular myocytes were recorded using whole-cell patch clamp technique. STZ-injected rats exhibited hyperglycemia, reduced body weight gain, and elevated plasma ET-1 concentration, indicative of diabetes induction. Ventricular myocytes isolated from diabetic rats exhibited prolonged action potential and reduced all three types of outward K+ currents. Resting membrane potential, height of action potential, and L-type Ca2+ current were not altered in diabetic myocytes. In vivo chronic treatment of diabetic rats with bosentan significantly augmented K+ currents and reversed action potential prolongation in ventricular myocytes. On the other hand, bosentan treatment had no detectable effect on the electrophysiological properties in control myocytes. In addition, bosentan had no effect on Ltype Ca2+ currents in both control and diabetic myocytes. Our data suggest that altered electrophysiological properties in ventricular myocytes were largely resulted from augmented ET-1 system in diabetic animals.


Patient Satisfaction with Pre-Hospital Emergency Services. A Qualitative Study Comparing Professionals' and Patients' Views.
Objective: To describe patient satisfaction with pre-hospital emergency knowledge and determine if patients and professionals share a common vision on the satisfaction predictors. Methods: A qualitative study was conducted in two phases. First, a systematic review following the PRISMA protocol was carried out searching publications between January 2000 and July 2016 in Medline, Scopus, and Cochrane. Second, three focus groups involving professionals (advisers and healthcare providers) and a total of 79 semi-structured interviews involving patients were conducted to obtain information about what dimensions of care were a priority for patients. Results: Thirty-three relevant studies were identified, with a majority conducted in Europe using questionnaires. They pointed out a very high level of satisfaction of callers and patients. Delay with the assistance and the ability for resolution of the case are the elements that overlap in fostering satisfaction. The published studies reviewed with satisfaction neither the overall care process nor related the measurement of the real time in responding to an emergency. The patients and professionals concurred in their assessments about the most relevant elements for patient satisfaction, although safety was not a predictive factor for patients. Response capacity and perceived capacity for resolving the situation were crucial factors for satisfaction. Conclusions: Published studies have assessed similar dimensions of satisfaction and have shown high patient satisfaction. Expanded services resolving a wide number of issues that can concern citizens are also positively assessed. Delays and resolution capacity are crucial for satisfaction. Furthermore, despite the fact that few explanations may be given due to a lack of face-to-face attention, finding the patient's location, taking into account the caller's emotional needs, and maintaining phone contact until the emergency services arrive are high predictors of satisfaction.


Double-polyelectrolyte, like-charged amphiphilic diblock copolymers: swollen structures and pH- and salt-dependent lyotropic behavior.
We consider a symmetrical poly(styrene- stat-(acrylic acid))- block-poly(acrylic acid), i.e., PSAA- b-PAA, diblock copolymer, with a molar fraction phi AA = 0.42 of acrylic acid, in the more hydrophobic PSAA statistical first block. We investigate its structural behavior at constant concentration in water using small-angle neutron scattering (SANS) by varying (i) the ionization of its acrylic acid motives via the pH by adding NaOH and (ii) the ionic strength of the solution by increasing the NaCl salt concentration c S. We present the resulting morphological phase diagram {pH, c S}, in which we identified two different lamellar phases presenting a smectic long-range order at small-to-intermediate ionizations and a spherical phase with a liquid-like short-range order at larger ionization. In the low-ionization regime, the first lamellar phase comprises a water-free PSAA lamellar core surrounded by a dense poly(acrylic acid) brush swollen with water. Its mostly hydrophobic core still being glassy, this phase is unable to reorganize and is frozen in. A detailed analysis of the SANS data shows the osmotic nature of the polyelectrolyte brush, in which the Na+ counterions are confined so that local electroneutrality is satisfied. Above the pH at which the PSAA statistical block starts ionizing, the PSAA lamellar core melts. The second lamellar phase identified then comprises a PSAA core thinner than that of the frozen-in previous phase, implying a significant increase of the core/water interface and a decrease of the brush surface density. The transition from the first lamellar phase to the second one can be quantitatively shown to result from the balance between the two contributions: (i) the extra interfacial cost between the thinner core and water and (ii) the associated gain in entropy of mixing for the counterions confined inside the brush. At even higher ionization, the diblocks finally form spherical objects with a very small, pH-dependent aggregation number and reach an apparent onset of self-association. When the highest ionization investigated is reached, the cores of these final spherical core-shell objects are found to contain a significant amount of water. We thereby demonstrate that at constant concentration, pH, and ionic strength both trigger a transition from frozen to molten hydrophobic phases as well as unexpected morphological transitions.


III-V/silicon-on-Insulator nanophotonic cavities for optical network-on-chip.
We review some opto-electronic devices based on the III-V/SOI heterogeneous integration platform, including lasers, modulators, wavelength converters, and photo-detectors. All of them are critical components for future on-chip interconnect and optical network-on-chip. The footprints of such devices are kept small by employing micro-cavity based structures. We give an overview of the device performances. The advantages over the all-silicon based devices are also discussed.


Functional language networks in sedentary and physically active older adults.
Functional magnetic resonance imaging (fMRI) studies have identified consistent age-related changes during various cognitive tasks, such that older individuals display more positive and less negative task-related activity than young adults. Recently, evidence shows that chronic physical exercise may alter aging-related changes in brain activity; however, the effect of exercise has not been studied for the neural substrates of language function. Additionally, the potential mechanisms by which aging alters neural recruitment remain understudied. To address these points, the present study enrolled elderly adults who were either sedentary or physically active to characterize the neural correlates of language function during semantic fluency between these groups in comparison to a young adult sample. Participants underwent fMRI during semantic fluency and transcranial magnetic stimulation to collect the ipsilateral silent period, a measure of interhemispheric inhibition. Results indicated that sedentary older adults displayed reductions in negative task-related activity compared to the active old group in areas of the attention network. Longer interhemispheric inhibition was associated with more negative task-related activity in the right and left posterior perisylvian cortex, suggesting that sedentary aging may result in losses in task facilitatory cortical inhibition. However, these losses may be mitigated by regular engagement in physical exercise.


Bioinformatics analysis of sex differences in arrhythmogenic right ventricular cardiomyopathy.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease that exhibits sex differences on clinical presentation. The present study aimed to investigate the sex differences associated with ARVC by conducting an integrated bioinformatics analysis. The GSE29819 gene expression dataset was downloaded from the Gene Expression Omnibus database. The online analytical tool GEO2R was then used to screen for differentially expressed genes (DEGs), which were subsequently processed using enrichment analysis and protein‑protein interaction (PPI) network construction. Functional annotation of the DEGs was determined using ClueGO. The PPI network was constructed with Search Tool for the Retrieval of Interacting Genes, and was visualized with Cytoscape to identify the modules and hub genes. Compared with the female group, a total of 1,188 DEGs, of which 915 were upregulated and 273 were downregulated, were identified in the male group. The enrichment analysis revealed that in KEGG pathways, the upregulated DEGs were substantially enriched in the 'nicotine addiction' pathways, whereas the downregulated DEGS were mainly enriched in the 'ECM‑receptor interaction' and 'protein digestion and absorption' pathways. The PPI network contained 899 nodes and 1,627 edges, among which four significant modules were identified. In addition, kininogen 1, lysophosphatidic acid receptor 5, formyl peptide receptor (FPR) 2, adenylate cyclase 2, γ‑aminobutyric acid type B receptor subunit 2, FPR1, hydroxycarboxylic acid receptor 1, prostaglandin E receptor 3, cannabinoid receptor 1 and proenkephalin were identified as the top 10 hub genes. The key genes and related pathways identified in this study provide genetic insight into the diversity in phenotypes between female and male patients with ARVC, and may facilitate therapeutic individualization.


Locking Plate Fixation with Multiple Telescoping Sliding Screws for Femoral Neck Fractures.
Non-displaced femoral neck fractures are mostly treated with internal fixation, while in dis-placed fractures this surgical option is under debate and the benefits are still not clear. The purpose of this study was to identify the factors that affect the treatment of non-displaced and displaced hip fractures using a head-preserving plate. From August 2011 to May 2015, we reviewed eighty-two adult patients who had sustained undisplaced and displaced intracapsular femoral neck fracture treated with a locking plate system with telescoping sliding screws. Fracture reduction, healing rate and implant related complications were primary objectives. Other complications (e.g. avascular necrosis, nonunion, hematoma, infection) and revision surgery were recorded as well. According to the Garden classification system, a total of 51.2% fractures were classified as non-displaced (type 1 and 2) and 48.8% were displaced fractures (type 3 and 4). Anatomic reduction was achieved in 58.5% and valgus in 41.5% of patients and it did not influence the healing. Varus reduction was not observed in any case. The total average complication rate was 18.1%, where screw cutout was the most frequent complication (8.5%). The timing of surgery did not affect the healing of femoral neck fractures. Age over 60 years combined with a displaced fracture was associated with impaired healing potential and a higher complication rate. Revision surgery was performed in 17.1% of patients, mainly those with displaced fractures. 1. The use of a locking plate system with telescoping sliding screws was associated with lower rates of postoperative complications in undisplaced, but also in displaced femoral neck fractures in patients younger 60 years. 2. Patients over 60 years with displaced fractures were more likely to have healing problems and implant failure.


Glycemic control of apoptosis in the pancreatic beta cell: danger of extremes?
Excessive formation of oxygen radicals is a well-established mediator of hyperglycemic damage in diabetes to a wide range of tissues, such as neurons, retinal cells, and vascular endothelium. Increased oxygen radical formation is generally considered a toxic side effect of excessive rates of mitochondrial oxidative metabolism and electron transport in high glucose-exposed cells. Along the same line, metabolic oxidative stress is currently also regarded as crucial mediator of beta cell dysfunction and apoptosis under hyperglycemic conditions. Here the authors argue that a healthy beta cell is well equipped to deal adequately with elevated glucose metabolic rates, and demonstrate that decreased glucose catabolism leads to ROS production and apoptosis. They therefore propose that adverse metabolic conditions in poorly controlled diabetes (hyperglycemia and/or dyslipidemia) or genetic defects could decrease the viability of beta cells by interfering with normal glucose sensing and metabolism, rather than by overactivating it. This view is supported by the fragmentary data currently available on the pathways for hypergycemic and hypoglycemic beta cell death.


An outbreak of ertapenem-resistant, carbapenemase-negative and porin-deficient ESBL-producing Klebsiella pneumoniae complex.
Carbapenem-resistant Klebsiella pneumoniae is an emerging healthcare-associated pathogen with dynamic molecular epidemiology. This study presents a retrospective analysis of the distribution and antibiotic resistance patterns of ertapenem-resistant ESBL-producing K. pneumoniae strains recovered during an outbreak from 2012 to 2014 in a Croatian University hospital. We aimed to estimate genetic relatedness of clinical isolates and underlying mechanisms that conferred the ertapenem-resistant phenotype. Expression analysis of genes involved in the antibiotic resistance showed reduced expression of major non-selective porin channel OmpK35. Reduced expression of OmpK36 porin channel in isolates resistant to at least one more carbapenem, apart from the ertapenem, was found to a lesser degree. Pulsed-field gel electrophoresis analysis of genomic DNA revealed that almost all isolates belonged to the same genetic clone. Caution regarding ertapenem-resistant, carbapenemase-negative porin-deficient mutants of K. pneumoniae is required as they are widespread, and under selective pressure this could result in a local clonal outbreak.


Effect of Different Amendments on Growing of Canna indica L. Inoculated with AMF on Mining Substrate.
Canna indica L. (CiL) was used here in phytoremediation of mining soils. Our work evaluated the effect of AMF (i) on the growth and (ii) on the uptake of heavy metals (HM). The tests were conducted in the greenhouse on mining substrates collected from the Kettara mine (Morocco). The mine soil was amended by different proportions of agricultural soil and compost and then inoculated with two isolates of AMF (IN1) and (IN2) of different origins. After six months of culture, the results show that on mining soils (100%) only AMF (IN2) was able to colonize the roots of CiL with a frequency of 40±7% and an intensity of 6.5±1.5%. Also, the lowest values of shoot and root dry biomass are obtained on these mining soils with respectively 0.30 g and 0.27 g. In contrast, the accumulation of HM was higher and reached more than 50% of that contained in the mining soils, the highest values with 138 mg kg(-1) Cu2+, Zn2+ 270 mg kg(-1) and 1.38 mg kg(-1) Cd was recorded. These results indicate that the colonization of CiL roots by AMF (IN2) could significantly improve its potential to be used in phytoremediation of polluted soil.


Diagnostic and therapeutic approach to hepatocellular carcinoma in the USA.
It is now apparent that hepatocellular carcinoma is occurring with increasing frequency in the USA. This mirrors a trend that occurred in Japan approximately 10 years earlier. Although the approach to diagnosis and treatment are similar in Japan and the USA, there are some differences. Thus, imaging is the primary modality of diagnosis and computed tomography and magnetic resonance imaging are favored over ultrasound. Liver transplantation is an important modality oftherapy, which is associated with excellent survival and, with the introduction of the Model for End-Stage Liver Disease (MELD) system, there has been a sharp rise in liver transplants performed for hepatocellular carcinoma since 2002.


Plastome phylogenomics, systematics, and divergence time estimation of the Beilschmiedia group (Lauraceae).
Intergeneric relationships of the Beilschmiedia group (Lauraceae) remain unresolved, hindering our understanding of their classification and evolutionary diversification. To remedy this, we sequenced and assembled complete plastid genomes (plastomes) from 25 species representing five genera spanning most major clades of Beilschmiedia and close relatives. Our inferred phylogeny is robust and includes two major clades. The first includes a monophyletic Endiandra nested within a paraphyletic Australasian Beilschmiedia group. The second includes (i) a subclade of African Beilschmiedia plus Malagasy Potameia, (ii) a subclade of Asian species including Syndiclis and Sinopora, (iii) the lone Neotropical species B. immersinervis, (iv) a subclade of core Asian Beilschmiedia, sister to the Neotropical species B. brenesii, and v) two Asian species including B. turbinata and B. glauca. The rampant non-monophyly of Beilschmiedia we identify necessitates a major taxonomic realignment of the genus, including but not limited to the mergers of Brassiodendron and Sinopora into the genera Endiandra and Syndiclis, respectively. Along these lines, the high degree of continental, clade-wide endemism we identify suggests that geographical distribution may be a good proxy for delineating taxa within this group. Our molecular divergence time estimates indicate that stem Beilschmiedia group members date to the Early Eocene (~50 Ma); their crown age dates to the Eocene-Oligocene boundary (~34 Ma). These findings contradict older estimates of the group and support mounting evidence that the origin and diversification of many pantropical angiosperm clades are not easily attributed to strict western Gondwanan vicariance. Finally, our study highlights the phylogenetic utility of plastomes in Lauraceace, and lays a solid foundation for future phylogenomic and biogeographic investigations within the family.


Circular single-stranded RNA replicon in Saccharomyces cerevisiae.
Circular RNA replicons have been reported in plants and, in one case, in animal cells. We describe such an element in yeast. In certain yeast strains, a 20S RNA species appears on transfer of cells to acetate medium. This phenotype shows cytoplasmic (non-Mendelian) inheritance and the 20S RNA is associated with 23-kDa protein subunits as a 32S particle. We demonstrate that yeast 20S RNA is an independent replicon with no homology to host genomic, mitochondrial, or 2-microns plasmid DNA or to the L-A, L-BC, or M1 double-stranded RNA viruses of yeast. The circularity of the 20S RNA is shown by the apparent absence of 3' and 5' ends, by two-dimensional gel electrophoresis, and by electron microscopy. Replication of yeast 20S RNA proceeds through an RNA-RNA pathway, and a 10,000-fold amplification occurs on shift to acetate medium. The copy number of 20S RNA is also reduced severalfold by the SKI gene products, a host antiviral system that also lowers the copy numbers of yeast double-stranded RNA viruses. Yeast 20S RNA and the hepatitis delta virus show some similarities.


Identification of Tartary Buckwheat (Fagopyrum tataricum (L.) Gaertn) and Common Buckwheat (Fagopyrum esculentum Moench) Using Gas Chromatography-Mass Spectroscopy-Based Untargeted Metabolomics.
Tartary buckwheat has attracted more attention than common buckwheat due to its unique chemical composition and higher efficacy in the prevention of various diseases. The content of flavonoids in Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is higher than that in common buckwheat (Fagopyrum esculentum Moench). However, the processing process of Tartary buckwheat is complex, and the cost is high, which leads to the frequent phenomenon of common buckwheat counterfeiting and adulteration in Tartary buckwheat, which seriously damages the interests of consumers and disrupts the market order. In order to explore a new and simple identification method for Tartary buckwheat and common buckwheat, this article uses metabolomics technology based on GC-MS to identify Tartary buckwheat and common buckwheat. The results show that the PLS-DA model can identify Tartary buckwheat and common buckwheat, as well as Tartary buckwheat from different regions, without an over-fitting phenomenon. It was also found that ascorbate and aldarate metabolism was the main differential metabolic pathway between Tartary buckwheat and common buckwheat, as well as the amino acids biosynthesis pathway. This study provides a new attempt for the identification of Tartary buckwheat and common buckwheat for the quality control of related agricultural products.


Genetic requirements for Staphylococcus aureus nitric oxide resistance and virulence.
Staphylococcus aureus exhibits many defenses against host innate immunity, including the ability to replicate in the presence of nitric oxide (NO·). S. aureus NO· resistance is a complex trait and hinges on the ability of this pathogen to metabolically adapt to the presence of NO·. Here, we employed deep sequencing of transposon junctions (Tn-Seq) in a library generated in USA300 LAC to define the complete set of genes required for S. aureus NO· resistance. We compared the list of NO·-resistance genes to the set of genes required for LAC to persist within murine skin infections (SSTIs). In total, we identified 168 genes that were essential for full NO· resistance, of which 49 were also required for S. aureus to persist within SSTIs. Many of these NO·-resistance genes were previously demonstrated to be required for growth in the presence of this immune radical. However, newly defined genes, including those encoding SodA, MntABC, RpoZ, proteins involved with Fe-S-cluster repair/homeostasis, UvrABC, thioredoxin-like proteins and the F1F0 ATPase, have not been previously reported to contribute to S. aureus NO· resistance. The most striking finding was that loss of any genes encoding components of the F1F0 ATPase resulted in mutants unable to grow in the presence of NO· or any other condition that inhibits cellular respiration. In addition, these mutants were highly attenuated in murine SSTIs. We show that in S. aureus, the F1F0 ATPase operates in the ATP-hydrolysis mode to extrude protons and contribute to proton-motive force. Loss of efficient proton extrusion in the ΔatpG mutant results in an acidified cytosol. While this acidity is tolerated by respiring cells, enzymes required for fermentation cannot operate efficiently at pH ≤ 7.0 and the ΔatpG mutant cannot thrive. Thus, S. aureus NO· resistance requires a mildly alkaline cytosol, a condition that cannot be achieved without an active F1F0 ATPase enzyme complex.


An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump.
Bacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics from the cell. In Gram-negative bacteria, some of these pumps form multi-protein assemblies that span the cell envelope. Here, we report the near-atomic resolution cryoEM structures of the Escherichia coli AcrAB-TolC multidrug efflux pump in resting and drug transport states, revealing a quaternary structural switch that allosterically couples and synchronizes initial ligand binding with channel opening. Within the transport-activated state, the channel remains open even though the pump cycles through three distinct conformations. Collectively, our data provide a dynamic mechanism for the assembly and operation of the AcrAB-TolC pump.


COVID-19 Vaccination Associated With Reduced Postoperative SARS-CoV-2 Infection and Morbidity.
The purpose of this study was to determine the effect of COVID-19 vaccination on postoperative mortality, pulmonary and thrombotic complications, readmissions and hospital lengths of stay among patients undergoing surgery in the United States. While vaccination prevents COVID-19, little is known about its impact on postoperative complications. This is a nationwide observational cohort study of all 1,255 Veterans Affairs facilities nationwide. We compared patients undergoing surgery at least 2 weeks after their second dose of the Pfizer BioNTech or Moderna vaccines, to contemporary propensity score matched controls. Primary endpoints were 30-day mortality and postoperative COVID-19 infection. Secondary endpoints were pulmonary or thrombotic complications, readmissions, and hospital lengths of stay. 30,681 patients met inclusion criteria. After matching, there were 3,104 in the vaccination group (1,903 received the Pfizer BioNTech, and 1,201 received the Moderna vaccine) and 7,438 controls. Full COVID-19 vaccination was associated with lower rates of postoperative 30-day COVID-19 infection (Incidence Rate Ratio and 95% confidence intervals, 0.09 [0.01,0.44]), pulmonary complications (0.54 [0.39, 0.72]), thrombotic complications (0.68 [0.46, 0.99]) and decreased hospital lengths of stay (0.78 [0.69, 0.89]). Complications were also low in vaccinated patients who tested COVID-19 positive before surgery but events were too few to detect a significant difference compared to controls. COVID-19 vaccination is associated with lower rates of postoperative morbidity. The benefit is most pronounced among individuals who have never had a COVID-19 infection before surgery.


In vitro evaluation of shear bond strengths and in vivo analysis of bond survival of indirect-bonding resins.
In this study we evaluate the shear bond strengths (SBS) of indirect-bonding systems available on the market. For the in vitro study, 60 extracted premolars were divided into three groups. In indirect group I, the brackets were bonded to models using Therma Cure laboratory resin and transferred to the teeth using Custom IQ resin for indirect bonding. For indirect group II, the teeth were attached to models using Transbond XT and transferred using Sondhi Rapid Set. In the direct-bonding group, the brackets were bonded to teeth directly using Transbond XT The SBS were evaluated, and the comparisons were made. In the in vivo study, left half of the upper arch and right half of the lower arch were bonded using Sondhi's indirect-bonding resin and right half of the upper arch and left half of the lower arch were bonded using Therma Cure as a laboratory resin and Custom IQ as a clinical bonding resin. The failure rates of the brackets were followed for nine months. Analysis of variance and Tukey tests were performed. Mean SBS values (MPa) were 10.3 +/- 4.2, 6.1 +/- 1.6, and 12.8 +/- 5.4 for the indirect groups I and II and for the direct-bonding group, respectively. There were no significant differences between indirect group I and direct group (P > .05), whereas both yielded significantly higher SBS values compared with indirect group II. In vivo bond survival evaluation showed no differences between the two indirect-bonding systems available.


Healthy preterm newborns: Altered innate immunity and impaired monocyte function.
Birth prior to 37 completed weeks of gestation is referred to as preterm (PT). Premature newborns are at increased risk of developing infections as neonatal immunity is a developing structure. Monocytes, which are key players after birth, activate inflammasomes. Investigations into the identification of innate immune profiles in premature compared to full-term infants are limited. Our research includes the investigation of monocytes and NK cells, gene expression, and plasma cytokine levels to investigate any potential differences among a cohort of 68 healthy PT and full-term infants. According to high-dimensional flow cytometry, PT infants have higher proportions of CD56+/- CD16+ NK cells and immature monocytes, and lower proportions of classical monocytes. Gene expression revealed lower proportions of inflammasome activation after in vitro monocyte stimulation and the quantification of plasma cytokine levels expressed higher concentrations of alarmin S100A8. Our findings suggest that PT newborns have altered innate immunity and monocyte functional impairment, and pro-inflammatory plasmatic profile. This may explain PT infants' increased susceptibility to infectious disease and should pave the way for novel therapeutic strategies and clinical interventions.


Allergy to ortho-phthalaldehyde in the healthcare setting: advice for clinicians.
This study summarizes and reviews the available health information on ortho-phthalaldehyde (OPA), a recently introduced and widespread disinfectant for heat-sensitive medical equipment, particularly focusing on its possible immunological effects in the healthcare setting. OPA properties derived from laboratory and clinical studies, and in vivo and in vitro tests for the diagnosis of OPA allergy are described. The available evidence suggests the spreading of OPA as disinfectant in endoscopy units despite the little available scientific evidence on its safety. Indeed, some papers reported on serious adverse reactions to OPA in patients and, to a lesser extent, in exposed workers, and in vivo studies suggested that OPA is a dermal and respiratory sensitizer. Finally, until more definite safety data become available only suggestions on possible preventive measures can be provided.


Controlling the synthesis and assembly of fluorescent Au/Ag alloy nanoclusters.
Self-assembly of water-soluble fluorescent thiolated Au/Ag alloy NCs into 1D nanostructure in water is demonstrated. Fluorescent Au/Ag alloy NCs with high stability were synthesized through galvanic replacement, starting from nonemissive and unstable AgNC precursors. Then a facile ultrasound method was used to induce a thiolate-driven self-assembly process.


Influences of diurnal sampling bias on fixed-point monitoring of plankton biodiversity determined using a massively parallel sequencing-based technique.
In this study, we investigated the influence of diurnal sampling bias on the community structure of plankton by comparing the biodiversity among seawater samples (n=9) obtained every 3h for 24h by using massively parallel sequencing (MPS)-based plankton monitoring at a fixed point conducted at Himedo seaport in Yatsushiro Sea, Japan. The number of raw operational taxonomy units (OTUs) and OTUs after re-sampling was 507-658 (558 ± 104, mean ± standard deviation) and 448-544 (467 ± 81), respectively, indicating high plankton biodiversity at the sampling location. The relative abundance of the top 20 OTUs in the samples from Himedo seaport was 48.8-67.7% (58.0 ± 5.8%), and the highest-ranked OTU was Pseudo-nitzschia species (Bacillariophyta) with a relative abundance of 17.3-39.2%, followed by Oithona sp. 1 and Oithona sp. 2 (Arthropoda). During seawater sampling, the semidiurnal tidal current having an amplitude of 0.3ms(-1) was dominant, and the westward residual current driven by the northeasterly wind was continuously observed during the 24-h monitoring. Therefore, the relative abundance of plankton species apparently fluctuated among the samples, but no significant difference was noted according to G-test (p>0.05). Significant differences were observed between the samples obtained from a different locality (Kusuura in Yatsushiro Sea) and at different dates, suggesting that the influence of diurnal sampling bias on plankton diversity, determined using the MPS-based survey, was not significant and acceptable.


Clinicopathological study and management of peripheral soft tissue tumours.
Soft-tissue tumours comprise a large heterogeneous group of mesenchymal neoplasms that is classified according to their normal tissue counterpart. They are ubiquitous in nature and can pose a challenge in terms of diagnosis and therefore, in their management. Biopsy findings bear direct implications on the treatment outcomes. The current study was conducted to understand various modes of clinical presentation, diagnostic modalities and to correlate them with operative findings, to delineate the different treatment modalities for patients with soft tissue tumours. We also assessed the risk factors and complications associated with soft tissue tumours. This was a prospective study conducted at a rural teaching hospital in India. Accurate history was elicited from patients with peripheral soft tissue tumours and a thorough physical examination was done. The patient demographics were noted. The clinical parameters assessed included location and size of swelling, any associated pain, neurovascular symptoms, presence of any deformity and medical risk factors. To diagnose the type of swelling, biopsy was done. All swellings were excised, and based on the diagnosis, additional therapeutic measures were employed. Post-operative complications and hospital stay were recorded. A total of 74 patients were included in the study, with male to female ratio of 1:1 and average age of 37.96 years. All of them presented with a swelling. The lower extremities and trunk were the most common sites, with each comprising about 25%. The size of tumour varied from 2 to 10 cm in diameter. Seventy one were benign and three were malignant. About one third of patients complained of pain. Comorbid illnesses were present in three patients. For benign tumours, simple excision was done, while for the malignant ones, multimodal therapeutic approach was taken. Post-operatively, two patients developed skin ulceration over the tumour, and six had wound infection. Most soft tissue tumours encountered in clinical practice are benign, of which lipoma is the commonest. While simple excision suffices for most benign tumours, a more aggressive treatment approach is required for their malignant counterparts.


Identification of Genes and MicroRNAs Affecting Pre-harvest Sprouting in Rice (Oryza sativa L.) by Transcriptome and Small RNAome Analyses.
Pre-harvest sprouting (PHS) is one of the primary problems associated with seed dormancy in rice (Oryza sativa L.). It causes yield loss and reduces grain quality under unpredictable humid conditions at the ripening stage, thus affecting the economic value of the rice crop. To resolve this issue, understanding the molecular mechanism underlying seed dormancy in rice is important. Recent studies have shown that seed dormancy is affected by a large number of genes associated with plant hormone regulation. However, understanding regarding the effect of heat stress on seed dormancy and plant hormones is limited. This study compared the transcriptome and small RNAome of the seed embryo and endosperm of two contrasting japonica rice accessions, PHS susceptible (with low seed dormancy) and PHS resistant (with high seed dormancy), at three different maturation stages. We found that 9,068 genes and 35 microRNAs (miRNAs) were differentially expressed in the embryo, whereas 360 genes were differentially expressed in the endosperm. Furthermore, we identified and verified the candidate genes associated with seed dormancy and heat stress-related responses in rice using quantitative real-time PCR. We newly discovered eight hormone-related genes, four heat shock protein-related genes, and two miRNAs potentially involved in PHS. These findings provide a strong foundation for understanding the dynamics of transcriptome and small RNAome of hormone- and heat stress-related genes, which affect PHS during seed maturation.


Prussian Blue Analogue with Fast Kinetics Through Electronic Coupling for Sodium Ion Batteries.
Alternative battery systems based on the chemistry of sodium are being considered to offer sustainability and cost-effectiveness. Herein, a simple and new method is demonstrated to enable nickel hexacyanoferrate (NiHCF) Prussian blue analogues (PBA) nanocrystals to be an excellent host for sodium ion storage by functionalization with redox guest molecule. The method is achieved by using NiHCF PBA powders infiltrated with the 7,7,8,8-tetracyanoquinododimethane (TCNQ) solution. Experimental and ab initio calculations results suggest that TCNQ molecule bridging with Fe atoms in NiHCF Prussian blue analogue leads to electronic coupling between TCNQ molecules and NiHCF open-framework, which functions as an electrical highway for electron motion and conductivity enhancement. Combining the merits including high electronic conductivity, open framework structure, nanocrystal, and interconnected mesopores, the NiHCF/TCNQ shows high specific capacity, fast kinetics and good cycling stability, delivering a high specific capacity of 35 mAh g-1 after 2000 cycles, corresponding a capacity loss of 0.035% decay per cycle.


Selective membrane protein internalization accompanies movement from the endoplasmic reticulum to the protein storage vacuole pathway in Arabidopsis.
In plant cells, certain membrane proteins move by unknown mechanisms directly from the endoplasmic reticulum (ER) to prevacuolar or vacuole-like organelles where membrane is internalized to form a dense, lattice-like structure. Here, we identify a sequence motif, PIEPPPHH, in the cytoplasmic tail of a membrane protein that directs the protein from the ER to vacuoles where it is internalized. A type II membrane protein in Arabidopsis thaliana, (At)SRC2 (for Soybean Gene Regulated by Cold-2), binds specifically to PIEPPPHH and moves from the ER to the same vacuoles where it is internalized. Not all proteins that move in this pathway are internalized because another Arabidopsis type II membrane protein, (At)VAP (for Vesicle-Associated Protein), localizes to the same organelles but remains exposed on the limiting membrane. The identification of (At)SRC2 and its preference for interaction with a targeting motif specific for the ER-to-vacuole pathway may provide tools for future dissection of mechanisms involved in this unique trafficking system.


Avian thermoregulation in the heat: resting metabolism, evaporative cooling and heat tolerance in Sonoran Desert songbirds.
We examined thermoregulatory performance in seven Sonoran Desert passerine bird species varying in body mass from 10 to 70 g - lesser goldfinch, house finch, pyrrhuloxia, cactus wren, northern cardinal, Abert's towhee and curve-billed thrasher. Using flow-through respirometry, we measured daytime resting metabolism, evaporative water loss and body temperature at air temperatures (Tair) between 30 and 52°C. We found marked increases in resting metabolism above the upper critical temperature (Tuc), which for six of the seven species fell within a relatively narrow range (36.2-39.7°C), but which was considerably higher in the largest species, the curve-billed thrasher (42.6°C). Resting metabolism and evaporative water loss were minimal below the Tuc and increased with Tair and body mass to maximum values among species of 0.38-1.62 W and 0.87-4.02 g H2O h-1, respectively. Body temperature reached maximum values ranging from 43.5 to 45.3°C. Evaporative cooling capacity, the ratio of evaporative heat loss to metabolic heat production, reached maximum values ranging from 1.39 to 2.06, consistent with known values for passeriforms and much lower than values in taxa such as columbiforms and caprimulgiforms. These maximum values occurred at heat tolerance limits that did not scale with body mass among species, but were ∼50°C for all species except the pyrrhuloxia and Abert's towhee (48°C). High metabolic costs associated with respiratory evaporation appeared to drive the limited heat tolerance in these desert passeriforms, compared with larger desert columbiforms and galliforms that use metabolically more efficient mechanisms of evaporative heat loss.


GEOGRAPHIC VARIATION AND PHENOTYPIC PLASTICITY OF NUMBER OF TRUNK VERTEBRAE IN SLENDER SALAMANDERS, BATRACHOSEPS (CAUDATA: PLETHODONTIDAE).
To understand the evolutionary significance of geographic variation, one must identify the factors that generate phenotypic differences among populations. I examined the causes of geographic variation in and evolutionary history of number of trunk vertebrae in slender salamanders, Batrachoseps (Caudata: Plethodontidae). Number of trunk vertebrae varies at many taxonomic levels within Batrachoseps. Parallel clines in number occur along an environmental gradient in three lineages in the Coast Ranges of California. These parallel clines may signal either adaptation or a shared phenotypically plastic response to the environmental gradient. By raising eggs from 10 populations representing four species of Batrachoseps, I demonstrated that number of trunk vertebrae can be altered by the developmental temperature; however, the degree of plasticity is insufficient to account for geographic variation. Thus, the geographic variation results largely from genetic variation. Number of trunk vertebrae covaries with body size and shape in diverse vertebrate taxa, including Batrachoseps. I hypothesize that selection for different degrees of elongation, possibly related to fossoriality, has led to the extensive evolution of number of trunk vertebrae in Batrachoseps. Analysis of intrapopulational variation revealed sexual dimorphism in both body shape and number of trunk vertebrae, but no correlation between these variables in either sex. Females are more elongate than males, a pattern that has been attributed to fecundity selection in other taxa. Patterns of covariation among different classes of vertebrae suggest that some intrapopulational variation in number results from changes in vertebral identity rather than changes in segmentation.


Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2-negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK).
Endocrine therapy continues to be the optimal systemic treatment for metastatic ER(+)HER2(-) breast cancer. The CDK4/6 inhibitor palbociclib combined with letrozole has recently been shown to significantly improve progression-free survival. Here we examined the cost-effectiveness of this regimen for the Swiss healthcare system. A Markov cohort simulation based on the PALOMA-1 trial (Finn et al. in Lancet Oncol 16:25-35, 2015) was used as the clinical course. Input parameters were based on summary trial data. Costs were assessed from the Swiss healthcare system perspective. Adding palbociclib to letrozole (PALLET) compared to letrozole monotherapy was estimated to cost an additional CHF342,440 and gain 1.14 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio (ICER) of CHF301,227/QALY gained. In univariate sensitivity analyses, no tested variation in key parameters resulted in an ICER below a willingness-to-pay threshold of CHF100,000/QALY. PALLET had a 0 % probability of being cost-effective in probabilistic sensitivity analyses. Lowering PALLET's price by 75 % resulted in an ICER of CHF73,995/QALY and a 73 % probability of being cost-effective. At current prices, PALLET would cost the Swiss healthcare system an additional CHF155 million/year. Palbociclib plus letrozole cannot be considered cost-effective for the first-line treatment of patients with metastatic breast cancer in the Swiss healthcare system.


Treatment and prevention of diaphragm fatigue using low-dose dopamine.
There is increasing evidence that diaphragm fatigue is a major cause of failure in weaning patients from mechanical ventilation. Patients in intensive care units are often administered dopamine to improve renal blood flow without regard to its effect on diaphragm blood flow. The aim of this study was to investigate if intravenous low-dose dopamine, equivalent to the dose used in intensive care units, can treat and prevent diaphragm fatigue. Diaphragm fatigue was produced in anesthetized rats by inspiratory resistance loading (IRL). The effect on diaphragm shortening, diaphragm blood flow, and aortic blood flow was determined. When diaphragm fatigue was attained, group I was given saline for 30 min while maintaining IRL. At the time of diaphragm fatigue, group II was given low-dose dopamine (2 microg/kg/min) for 30 min while maintaining IRL. In group III, dopamine administration was started before and continued throughout the period of IRL. Administering dopamine after the development of diaphragm fatigue (group II) increased diaphragm performance as measured by increased diaphragm shortening and was accompanied by an increased diaphragm blood flow. Administering dopamine prior to and throughout IRL (group III) prevented diaphragm fatigue. Low-dose dopamine can prevent and/or reverse diaphragm fatigue in rats without a significant change in aortic blood flow. This effect of dopamine may be due to increased oxygen delivery associated with the increased diaphragm blood flow, resulting in less free radical formation and thus less muscle damage.


Cryptosporidiosis occurrence in HIV+ patients attended in a hospital, Brazil.
Cryptosporidiosis occurrence was determined in HIV+ patient assisted in the Clinic of Infect-parasitic Diseases in a hospital of Nova Iguaçu, Rio de Janeiro, Brazil, in the period from July/1998 to March/1999. In order to research, seventy-five patient, carriers of diarrhea or not, were appraised. The samples of feces were collected and placed in saline solution with formaldehyde (5%). The Modified Ritchie technique was used for the oocysts research, and the smears were stained with Safranine O methylene blue. The results verified 9.33% of positive samples, with higher frequency of cases in patients of the masculine sex from 20 to 50 years old, however without significant difference.


Audiometry results and TEOAE and DPOAE amplitudes in men taking a phosphodiesterase type 5 inhibitor for erectile dysfunction.
We conducted a prospective study of transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) in men who were taking an oral phosphodiesterase type 5 (PDE5) inhibitor for erectile dysfunction. Our study group was made up of 30 men (60 ears), aged 34 to 60 years (mean: 50.9). They were randomly divided into three groups; 10 men were given sildenafil (Viagra) at 50 mg twice a week, 10 were given tadalafil (Cialis) at 20 mg twice a week, and 10 were given vardenafil (Levitra) at 20 mg twice a week. All patients took their drug for 3 weeks, for a total of 6 tablets for each patient. Audiometric tests and TEOAE and DPOAE measurements were performed before and after treatment. Post-treatment audiometry demonstrated improvement in hearing in all three groups. However, post-treatment TEOAE amplitudes and DPOAE amplitudes differed among the three groups; they were significantly higher in the sildenafil group at 1.0 kHz and the same in the tadalafil group; in the vardenafil group, the DPOAE amplitude was significantly lower at 3.0 kHz while there was no change in the TEOAE amplitude. We speculate that the possible mechanism for these findings is that PDE5 inhibitors block degradation of cyclic guanosine monophosphate (cGMP) and induce dilation of the cochlear microcirculation, resulting in an increase in cochlear blood flow. We also believe that the decrease in DPOAE amplitudes at 3.0 kHz seen in the vardenafil group may be related to an accumulation of nitric oxide/cGMP complex, which is toxic to the cochlea; however, since there was no change in TEOAE amplitude in the vardenafil group, this influence may be minimal. Further studies are needed to obtain a more comprehensive assessment of the effects of PDE5 inhibitors on hearing with the use of higher doses and longer durations of therapy.


Distribution of HBV genotypes and mutants among hepatitis B infected patients from northern Poland.
Hepatitis B virus (HBV) infection is one of the major global epidemiological problems. The aim of our study was to determine the distribution of HBV genotypes in Poland since the data concerning the spread of HBV viruses in the central-eastern region of Europe is still very limited. HBV DNA was extracted from 58 serum samples. To quantify the level of HBV DNA the Roche Amplicor HBV Monitor Assay was used. To genotype and assign HBV subtypes DNA sequencing methods were performed. The HBV virus from 43 serum samples from hepatitis B infected patients was genotype A (74.1%), 12 cases had genotype D (20.7%), and 3 had the rare in Europe genotype F (5.2%). Prediction of HBV serological subtypes based on HBsAg sequencing showed almost 100% occurrence of subtype adw2 in the group of genotype A samples, three different subtypes in genotype D (ayw2, ayw3, and ayw4), and equal distribution of subtype adw4q- in all 3 cases of genotype F, also the most prevalent subtype in the Amerindians. Our results coincide with the general European HBV prevalence. However, HBV genotype F, which is not a common genotype in European countries, was detected and so was relatively high occurrence of genotype D, which may reflect historical and ethnical migration events in Poland in the past.


Influence of the oxygen plasma parameters on the atomic layer deposition of titanium dioxide.
The influence of the oxygen plasma parameters on the morphology and optical properties of TiO2 thin films has been extensively analyzed in plasma enhanced atomic layer deposition (PEALD) processes. Crystalline aggregates with the anatase phase have been identified on the film surface at a low deposition temperature (down to 70 °C) under specific plasma conditions. Up to 70% surface coverage by anatase crystallites is obtained at low oxygen gas flow rates and high plasma power. The hillocks abundance is correlated with high ion flux and electron density and with the resulting enhanced ion bombardment of the surface. Altering the plasma conditions is an important parameter besides temperature to control the morphology of the titania film for specific applications such as photocatalysis or functional optical coatings. Specifically, photocatalytic titania coatings on polymer substrates could benefit of such low temperature PEALD processes with abundant anatase crystallites; whereas optical coatings require smooth, high refractive index titania as obtained with low plasma power and high oxygen flow rate.


Can the history of injury influence shoulder isokinetic torque parameters in volleyball players?
The aim of the present study was to compare shoulder internal rotator and external rotator isokinetic parameters in concentric and eccentric contractions between volleyball players with and without a history of shoulder injury. Thirty male volleyball players participated of this study, divided into two groups: with a history of injury (WHI) in the dominant shoulder (11 athletes; age: 19.4 ± 3.6 years) and no history of injury (NHI) (19 athletes; age: 18.3 ± 2.9 years). The peak torque (PT) and concentric (Con) and eccentric (Ecc) PT angles in internal (IR) and external rotation (ER) at velocities of 60 and 180°/s were measured. The conventional (Con_ER:Con_IR), functional spiking (Ecc_ER:Con_IR), and cocking ratios (Ecc_IR:Con_ER) were calculated. No significant differences were found between groups for PT and PT angle, or for conventional, functional spiking, and cocking ratios. However, the spiking ratio was considered low (0.87) in the WHI group. Moreover, for the spiking ratio in the WHI group, PT at 60°/s occurred at different angles. We conclude that previous injury in shoulder did not affect the peak torque, as well as conventional, spiking or cocking ratio. However, the PT angles at 60°/s used to calculate the spiking ratio shifted due the prior injury.