Steady-state kinetics of formaldehyde dehydrogenase and formate dehydrogenase from a methanol-utilizing yeast, Candida boidinii.
Initial velocity studies and product inhibition studies were conducted for the forward and reverse reactions of formaldehyde dehydrogenase (formaldehyde: NAD oxidoreductase, EC 22.214.171.124) isolated from a methanol-utilizing yeast Candida boidinii. The data were consistent with an ordered Bi-Bi mechanism for this reaction in which NAD+ is bound first to the enzyme and NADH released last. Kinetic studies indicated that the nucleoside phosphates ATP, ADP and AMP are competitive inhibitors with respect to NAD and noncompetitive inhibitors with respect to S-hydroxymethylglutathione. The inhibitions of the enzyme activity by ATP and ADP are greater at pH 6.0 and 6.5 than at neutral or alkaline pH values. The kinetic studies of formate dehydrogenase (formate:NAD oxidoreductase, EC 126.96.36.199) from the methanol grown C. boidinii suggested also an ordered Bi-Bi mechanism with NAD being the first substrate and NADH the last product. Formate dehydrogenase the last enzyme of the dissimilatory pathway of the methanol metabolism is also inhibited by adenosine phosphates. Since the intracellular concentrations of NADH and ATP are in the range of the Ki values for formaldehyde dehydrogenase and formate dehydrogenase the activities of these main enzymes of the dissimilatory pathway of methanol metabolism in this yeast may be regulated by these compounds.


Cost-sharing and horizontal compensation scheme of regional sulfur dioxide treatment: Evidence from China.
Establishing a reasonable cost-sharing and compensation mechanism for air pollution control is a prerequisite for realizing inter-regional cooperative treatment. Taking inter-provincial sulfur dioxide (SO2) emissions in China from 2005 to 2019 as the research object, this paper proposes a data-driven approach to establish a cost-sharing index system of regional SO2 treatment in four dimensions and construct a cost-sharing and compensation scheme using the entropy-TOPSIS method. The results revealed that there are significant spatial and temporal differences in the treatment cost of SO2 emission, and the total SO2 treatment costs at the national level increased first and then decreased during the study period, meanwhile, the regional SO2 treatment costs are much higher in the less economically developed regions such as the central and western regions than in economically developed eastern coastal regions. The design of the cost-sharing and compensation mechanism of SO2 treatment should consider the regional differences in abatement capacity, abatement potential, abatement responsibility, and development demands. The economically developed regions should share higher treatment costs according to their historical cumulative abatement responsibilities, and provide economic compensation and technical support to the less economically developed regions. Specifically, the marginal abatement cost in the more economically developed eastern region is much higher than that in the less economically developed central and western areas due to their large abatement responsibility and strong reduction capacity but insufficient abatement potential, so the eastern regions can transfer part of their abatement responsibility to the central and western regions using economic compensation. Reasonable cost sharing and horizontal compensation can help promote regional cooperation and synergistic management in air pollution abatement. Finally, corresponding policy recommendations are given to provide a decision basis for cross-regional cooperation in air pollution control.


Emergency medicine in Peru.
Emergency Medicine (EM) is a developing specialty in Peru, as is the case in many other countries around the world. The nation's first residency training program was started in 1993 at the Universidad Nacional Mayor de San Marcos (UNMSM). This description of the development, organization, challenges, and goals of the EM specialty in Peru is based on personal experience and communication with other specialists in the country.


[Application of electro-thermo-adhesion in hepatobiliary surgery].
Since 1999 yr. 283 laparoscopic operations were performed in the clinic for diseases of liver, biliary ducts, pancreas using electrothermoadhesion method, including 201 cholecystectomies, 62--in presence of hepatic cyst, 6--enucleation of hemangioms, 3--hepatic edge resection, 1--cholecystectomy, in 10 patients the puncture biopsy of pancreas was done.


Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.
The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.


Experience attributes and service quality dimensions of peer-to-peer accommodation in Malaysia.
This paper reports the empirical findings of experience attributes and service quality dimensions of peer-to-peer accommodation (P2P) in Malaysia. Data collection was conducted using in-depth interviews, which involved 10 P2P accommodation hosts and 15 P2P accommodation guests. Thematic analysis of the data guided by the concepts of service experience and service quality, revealed that P2P accommodation has four experience dimensions (property/accommodation, hosts, local people/culture, and location) and seven service quality dimensions (home facilities, personal advice, helpfulness, feeling welcome, responsiveness, reliability, and caring). These dimensions differentiate P2P accommodation from other types of accommodation, such as hotels, and are different from those of the SERVQUAL model. Subsequently, a new model, P2PSERVQUAL, is proposed for peer-to-peer accommodation. The findings add to the tourism and hospitality literature on experience attributes and service quality, with implications for the marketing and management of P2P accommodation.


Splenic cysts: a new approach to partial splenectomy.
Laparoscopic partial splenectomy of a splenic cyst in a 19-year-old female patient is discussed. We successfully performed a laparoscopic partial splenectomy and achieved meticulous hemostasis using an Endo-GIA stapling device. The patient tolerated the procedure well and was discharged on postoperative day 2. At this writing, she has been followed for 30 months without cyst recurrence. Minimally invasive surgery provides an alternative to conventional surgical procedures, with a short hospital stay and without the added morbidity of laparotomy.


Pre-operative erector spinae plane block should be considered a viable option for laparoscopic colectomies.
The Erector Spinae Plane (ESP) block is a recent development in the field of regional anaesthesia and has been increasingly explored for abdominal surgeries to reduce opioid use and improve pain control. Colorectal cancer is the commonest cancer in multi-ethnic Singapore and requires surgery for curative treatment. ESP is a promising alternative in colorectal surgeries, but few studies have evaluated its efficacy in such surgeries. Therefore, this study aims to evaluate the use of ESP blocks in laparoscopic colorectal surgeries to establish its safety and efficacy in this field. A prospective two-armed interventional cohort study comparing T8-T10 ESP blocks with conventional multimodal intravenous analgesia for laparoscopic colectomies was conducted in a single institution in Singapore. The decision for doing an ESP block versus conventional multimodal intravenous analgesia was made by a consensus between the attending surgeon and anesthesiologist. Outcomes measured were total intra-operative opioid consumption, post-operative pain control and patient outcome. Post-operative pain control was measured by pain score, analgesia use, and amount of opioids consumed. Patient outcome was determined by presence of ileus. A total of 146 patients were included, of which 30 patients received an ESP block. Overall, the ESP group had a significantly lower median opioid usage both intra-operatively and post-operatively (p = 0.031). Fewer patients required patient-controlled analgesia and rescue analgesia post-operatively for pain control (p < 0.001) amongst the ESP group. Pain scores were similar and post-operative ileus was absent in both groups. Multivariate analysis found that the ESP block had an independent effect on reducing intra-opioid consumption (p = 0.014). Multivariate analysis of post-operative opioid use and pain scores did not yield statistically significant results. The ESP block was an effective alternative regional anaesthesia for colorectal surgery that reduced intra-operative and post-operative opioid use while attaining satisfactory pain control.


Activity of glutamate and malate dehydrogenases in liver and kidneys of rats subjected to multiple exposures of mercuric chloride and sodium selenite.
Rats were subjected for 2 weeks to separate and combined exposures to mercuric chloride and sodium selenite at doses of 0.5 mg Hg/kg and 0.5 mg Se/kg. The content of mercury, selenium and protein as well as the activities of glutamate dehydrogenase (GLDH) and malate dehydrogenase (MDH) were determined in homogenates, mitochondria and intramitochondrial structures of the exposed animals. It was found that both separate and combined exposures of rats to mercuric chloride and sodium selenite inhibited GLDH activity and did not affect MDH activity in the examined organs. Mercury-selenium interaction brought about a decrease in the content of mercury in the intramitochondrial structures of kidneys and an increased accumulation of both elements in the outer and inner membranes of liver mitochondria. The biochemical mechanism of mercury-selenium interaction is discussed.


Biosimilars versus the originator of follitropin alfa: Randomized controlled trials are still the best way to evaluate their comparative effectiveness in assisted reproduction.
Biosimilars of follitropin alfa have been introduced in many countries as more affordable alternatives to the reference product for patients undergoing ovarian stimulation for assisted reproductive technology cycles. A recent meta-analysis, by reviewing available evidence originating from randomised controlled trials, has shown that based on the best available evidence, biosimilars of follitropin alfa are associated with lower live birth, ongoing and clinical pregnancy rates compared to the reference product. A subsequently published opinion paper challenges the methodology and results of this meta-analysis and suggests that these data should be ignored. In the present paper, it is clearly demonstrated why this criticism is largely unfounded and in stark contradiction with basic principles of evidence-based medicine. Furthermore, it is presented why the results of this meta-analysis provide the best available evidence to date and therefore the base that should inform clinical practice and, importantly, stimulate further research.


Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent.
Primary sclerosing cholangitis (PSC) is a rare, progressive liver disease characterized by cholestasis and bile duct fibrosis that has no accepted therapy known to delay or arrest its progression. We report a 23-year-old female patient who at age 14 was diagnosed with moderate pancolonic ulcerative colitis (UC) and at age 15 with small-duct PSC unresponsive to conventional therapy. The patient began single drug therapy with the antibiotic oral vancomycin (OVT) and achieved normalization of liver enzymes and resolution of UC symptoms with colonic mucosal healing. These improvements have persisted over 8 years. There has been no colon dysplasia, liver fibrosis or failure, bile duct stricture, or cancer. Of note, the patient's response was dependent on the brand of oral vancomycin capsule, as well as dose. This raised the questions of possible differences in bioequivalence of different commercial versions of the drug and whether this factor might play into the variability of efficacy seen in published trials. Evidence suggests that oral vancomycin both alters the intestinal microbiome and has immunomodulatory effects. Its striking effectiveness in this and other patients supports further investigation in randomized trials, with careful attention to its bioavailability profile in the gut.


Long term effect of local corticosteroid injection for carpal tunnel syndrome: a relation with electrodiagnostic severity.
Carpal tunnel syndrome (CTS) is a common entrapment neuropathy. A local corticosteroid injection at the carpal tunnel inlet is often given to reduce the signs and symptoms. The long term effect of a local corticosteroid injection is not known yet. The aims of the study were to assess the long term effect of a local corticosteroid injection and the rognostic factors. Assessment of 419 consecutive patients, seen between November 2004 and November 2007 at our Neurology out-patient clinic. After confirmation of the diagnosis CTS the treating neurologist decided on the patients eligibility for a local corticosteroid injection, containing 40 mg methylprednisolone. Local corticosteroid injection was given to 273 of the 419 patients with CTS (65%), 122 (29%) were treated surgically and 24 (6%) were treated by another therapy. Of the 273 patients long term follow-up was available for 211 (77%) patients. A beneficial effect of more than 6 months was seen in 132 patients (63%), longer than 12 months in 102 patients (48%), and longer than 18 months in 71 patients (34%). Only severity of electrodiagnostic testing was a predictor of outcome. The median time until treatment failure was 15 months for mild, 5 months for moderate and 4.5 months for severe CTS (logrank test p=0.02). Patients with an electrodiagnostically mild CTS (i.e., abnormal comparative tests or prolonged median DSL>3.5 ms but normal median DML) are good candidates for a local steroid injection with 50% having a good long term effect for more than 15 months. This study shows that the EMG severity of CTS is an important prognostic factor for the long term effect of a local steroid injection.


Development of silver oxide-loaded reduced graphene oxide nanohybrids for enhanced photocatalytic activity under visible light in aqueous solutions.
We report on the synthesis of silver oxide/reduced graphene oxide nanocomposites (Ag/rGO NCs) using a hydrothermal technique. This paper presents a simple method for synthesizing Ag/rGO hybrid nanocomposites, which can be used for environmentally treating hazardous organic pollutants. The photocatalytic degradation of model artificial Rhodamine B dye and bisphenol A was assessed under visible light illumination. The crystallinity, binding energy, and surface morphologies of the synthesized samples were determined. The silver oxide loading sample resulted in a decrease in the rGO crystallite size. SEM and TEM images demonstrate strong adhesion of the Ag NPs to the rGO sheets. XPS analysis validated the binding energy and elemental composition of the Ag/rGO hybrid nanocomposites. The objective of the experiment was to enhance the photocatalytic efficiency of rGO in the visible region using Ag nanoparticles. The synthesized nanocomposites in the visible region exhibited good photodegradation percentages of approximately 97.5% and 98.6% after 120 min of irradiation for pure rGO, Ag NPs, and Ag/rGO nanohybrid, respectively. Furthermore, the Ag/rGO nanohybrid maintained their degradation ability for up to three cycles. The synthesized Ag/rGO nanohybrid demonstrated enhanced photocatalytic activity, expanding their potential for environmental remediation. Based on the investigations, Ag/rGO nanohybrid proved to be an effective photocatalyst and holds promise as an ideal material for future applications in preventing water pollution.


A Statewide Elder Mistreatment Virtual Assessment Program: Preliminary Data.
To describe the Texas Elder Abuse and Mistreatment Institute Forensic Assessment Center Network (TEAM-FACN), a novel statewide elder mistreatment (EM) virtual assessment program using low-cost videophone technology and innovative web-based coordination to connect an Adult Protective Services (APS) agency and its clients, rural and urban, to a centralized geriatric and EM expert medical team for virtual in-home assessments. Descriptive. Community. APS clients aged 18 and older. Virtual and in-home assessments. Program use and type of services provided. In the first 8 months, 300 APS clients from all regions of the state were referred for assessment. Outcomes realized include a quadrupling in number of client assessments. TEAM-FACN physicians provided an average of 2 services, which included 216 mental health assessments, with 123 conducted virtually; 42 medical assessments; 45 guardianship filings; 5 employee misconduct registry reviews; and more than 230 interdisciplinary team meetings to discuss case findings, safety plans, and medical and social interventions. TEAM-FACN provides an innovative and viable way to increase access of urban and rural older and adults who are being mistreated to expert geriatric and EM protective service assessments. J Am Geriatr Soc 67:151-155, 2019.


2021 Consensus Pathway of the Taiwan Society of Cardiology on Novel Therapy for Type 2 Diabetes.
Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.


Flexible artificial Si-In-Zn-O/ion gel synapse and its application to sensory-neuromorphic system for sign language translation.
We propose a flexible artificial synapse based on a silicon-indium-zinc-oxide (SIZO)/ion gel hybrid structure directly fabricated on a polyimide substrate, where the channel conductance is effectively modulated via ion movement in the ion gel. This synaptic operation is possible because of the low-temperature deposition process of the SIZO layer (<150°C) and the surface roughness improvement of the poly(4-vinylphenol) buffer layer (12.29→1.81 nm). The flexible synaptic device exhibits extremely stable synaptic performance under high mechanical (bending 1500 times with a radius of 5 mm) and electrical stress (application of voltage pulses 104 times) without any degradation. Last, a sensory-neuromorphic system for sign language translation, which consists of stretchable resistive sensors and flexible artificial synapses, is designed and successfully evaluated via training and recognition simulation using hand sign patterns obtained by stretchable sensors (maximum recognition rate, 99.4%).


A virus-producing cell line developed by transformation of human parapharyngeal cells with SV40.
Normal cultures of epithelial appearance were initiated by trypsinization of a surgically resected, histologically normal branchial cyst. Cellular morphology was consistent with derivation from the stratified squamous epithelium of the cyst or from vascular endothelium, although electron micrographs of the cultured cells failed to show any junctional complexes. Infection with SV40 produced transformants which were also epithelioid in appearance. These grew vigorously for 22 to 50 population doublings (about 23 to 32 subcultures, depending upon regimen) and then became quiescent. During this evolution, virus was detectable at all stages by both direct isolation (cell extracts) and cocultivation with permissive cells. In two sublines in which selection for rapidly growing cell types occureed, virus was detected only by cocultivation. The work confirms that of others in the finding that normal human epithelial cells are susceptible to transformation by oncogenic viruses, but are apparently less responsive than are fibroblasts to such transforming agents. It also suggests that subcultivation techniques that maintain the populations of transformed cells at low density tend to select against cell strains that are continous producers of infectious virus.


Peripheral antinociception induced by ketamine is mediated by the endogenous opioid system.
Ketamine is a drug largely used in clinical practice as an anesthetic and it can also be used as an analgesic to manage chronic pain symptoms. Despite its interactions with several other signaling systems such as cholinergic, serotoninergic and adrenergic, it is accepted that NMDA receptor antagonism is the main mechanism of action of this drug. In this study we investigated the actions of endogenous opioids in the mechanism of peripheral analgesia induced by ketamine. The nociceptive threshold for mechanical stimuli was measured in Swiss mice using the Randall and Selitto test. The drugs used in this study were administered via intraplantar injection. Our results demonstrated that non selective opioid receptor antagonism (naloxone), selective μ- and δ-opioid receptors antagonism (clocinamox and naltrindole, respectively) but not κ-opioid receptor antagonism (nor-binaltorphimine NORBNI) antagonized ketamine-induced peripheral antinociception in a dose-dependent manner. In addition, administration of aminopeptidase inhibitor bestatin significantly potentiated ketamine-induced peripheral antinociception. Ketamine injection in the right hind paw induced β-endorphine synthesis in the epithelial tissue of the hindpaw. Together these results indicate a role for μ- and δ-opioid receptors and for the endogenous opioid β-endorphine increased synthesis in ketamine-induced peripheral analgesia mechanism of action.


Characteristics, staging and outcomes of differentiated thyroid cancer in patients with and without Graves' disease.
The incidence of thyroid cancer has increased over the last three decades with studies showing incidence of thyroid cancer is higher among patients with Graves' Disease (GD) when compared to Toxic multinodular goiter.1 We conducted a retrospective study to further investigate characteristics and outcomes in patients with thyroid cancer and GD. We retrospectively reviewed 62 patients with a diagnosis of Differentiated Thyroid Cancer (DTC). We compared age at diagnosis, type, size of tumor, radioactive iodine (RAI) use, and DTC recurrence amongst patients with GD, non-GD patients. We used Chi-square to test for independence among categorical variables at a nominal level of 0.05; comparison was based on t-test. Out of 62 patients, 29 patients had GD and DTC (47%). 94% had papillary thyroid cancer. Patients with GD were diagnosed with DTC at a younger age (mean 46 years) in comparison to patients without GD (mean 53 years). There was no difference in the type of DTC. Patients with GD had significantly smaller tumor size (mean size 1.035 cm; p value = 0.002), more Stage 1 and 2 compared to patients without GD (p-value = 0.009). Both groups of patients had similar rates of recurrence on follow up and RAI use. We found patients with GD had smaller tumor size, early-stage DTC when compared to patients without GD and potentially favorable prognosis. More data is needed to understand whether this is due to pathogenesis like Graves antibodies promoting tumor formation or merely earlier detection of DTC in GD.


The epidemiology of hospitalised wrist fractures in older people, New South Wales, Australia.
The epidemiology and trends in wrist fracture admissions to public and private acute hospitals in New South Wales (NSW), Australia, between July 1993 and June 2003 were examined using routinely collected hospital separations statistics. During the study period, the number of hospital separations for wrist fractures increased by 71% in men, an average yearly increase of 6.5%, and by 43% in women, an average yearly increase of 3.9%. A modest, but significant, increase in age-specific and age-standardised hospitalisation rates for wrist fractures was also observed. Whilst the majority of wrist fractures were due to falls, the proportion of falls-related wrist fractures decreased significantly over time. This decrease was more pronounced in males and was accompanied by a rise in the proportion of wrist fractures resulting from high energy mechanisms such as transport, violence and machinery-related incidents. The difference in hospitalised wrist fracture rates between men and women could not be explained solely on the basis of the role played by osteoporosis, indicating the need for more research to improve our understanding of the underlying factors of this type of fracture in older people.


Natural interferon enhances expression of placental alkaline phosphatase in human seminoma xenograft.
The purpose of this study was to investigate the effect of natural interferon (IFN) on the expression of placental alkaline phosphatase (PLAP) in a human seminoma xenograft in severe combined immunodeficient mice. Mice were injected intramuscularly with 3x10(5) U/mouse of IFN, twice a day, for five consecutive days. A significant increase in PLAP level of the xenografts followed IFN treatment. A radiolabeled anti-PLAP monoclonal antibody (MAb) was intravenously injected on the first day of IFN administration in order to determine if IFN has the potential to enhance the efficacy of an anti-PLAP MAb in the detection of seminoma. Enhanced retention of the anti-PLAP MAb was observed at 7 and 11 days after MAb administration. Thus, IFN treatment appears to have some effect on the efficacy of the anti-PLAP MAb in the detection of seminoma xenografts.


Identification and prediction model of placenta-brain axis genes associated with neurodevelopmental delay in moderate and late preterm children.
Moderate and late preterm (MLPT) birth accounts for the vast majority of preterm births, which is a global public health problem. The association between MLPT and neurobehavioral developmental delays in children and the underlying biological mechanisms need to be further revealed. The "placenta-brain axis" (PBA) provides a new perspective for gene regulation and risk prediction of neurodevelopmental delays in MLPT children. The authors performed multivariate logistic regression models between MLPT and children's neurodevelopmental outcomes, using data from 129 MLPT infants and 3136 full-term controls from the Ma'anshan Birth Cohort (MABC). Furthermore, the authors identified the abnormally regulated PBA-related genes in MLPT placenta by bioinformatics analysis of RNA-seq data and RT-qPCR verification on independent samples. Finally, the authors established the prediction model of neurodevelopmental delay in children with MLPT using multiple machine learning models. The authors found an increased risk of neurodevelopmental delay in children with MLPT at 6 months, 18 months, and 48 months, especially in boys. Further verification showed that APOE and CST3 genes were significantly correlated with the developmental levels of gross-motor domain, fine-motor domain, and personal social domain in 6-month-old male MLPT children. These findings suggested that there was a sex-specific association between MLPT and neurodevelopmental delays. Moreover, APOE and CST3 were identified as placental biomarkers. The results provided guidance for the etiology investigation, risk prediction, and early intervention of neurodevelopmental delays in children with MLPT.


Obstacles to using online health services among adults age 50 and up and the role of family support in overcoming them.
Using Online Health Services (OHS) could benefit older adults greatly and could also reduce the burden on the health system. Yet invisible obstacles or barriers appear to impede mass adoption of these services among this population group. The aim of the current research is to provide a qualitative picture of these invisible obstacles and to profile their main features, with special attention to the role of family members in supporting OHS use among this population group. This qualitative study entailed a series of in-depth, semi-structured, open phone interviews conducted with 31 individuals age 50 and up in Israel, who constituted a sample of OHS users and non-users among older adults. Four major themes and primary observations emerge from our data: 1. While older adults are aware of OHS to some extent, they often do not fully understand the specific benefits of using these services; 2. Older adults need to acquire much more experience with OHS use. OHS user interfaces still have a long way to go for older adults to feel comfortable using them. People age 50 and up seem to be less concerned about privacy and security issues than about seemingly more trivial issues such as recovering forgotten passwords; 3. Family members can play key roles in helping older adults adopt OHS by providing technical support as well as encouragement; 4. Older adults have worthwhile recommendations for innovations and policy improvements that would facilitate wider adoption of OHS. The results of the current study reveal important nuances regarding the importance of awareness, user interface and experience for OHS use among older adults, as well as the critical role of family members in OHS adoption. Based on these findings, we recommend the following: expanding advertising on media channels to emphasize the benefits of OHS use; improving HMO websites to make them more user-friendly for older people; developing HMO-run community OHS guidance programs geared to older people to reduce the gap between required skills and user competencies, thus enabling older people to benefit from OHS use.


Wife abuse: strategies for a therapeutic response.
An alarming number of women seek help for abuse from the health care establishment. Yet research shows that all too often, professionals fail to identify abuse and are nontherapeutic. This paper provides theoretical and research evidence to explore the factors that account for the less than helpful response of nurses toward wife-abuse victims. A feminist lens is used to explore strategies that can enable nurses to deal effectively with this health care dilemma.


Nintedanib and a bi-specific anti-VEGF/Ang2 nanobody selectively prevent brain metastases of lung adenocarcinoma cells.
Brain metastases (BM) are an ever-increasing challenge in oncology, threatening quality of life and survival of many cancer patients. The majority of BM originate from lung adenocarcinoma, and stage III patients have a risk of 40-50% to develop BM in the first years of disease onset. As therapeutic options are limited, prevention of their occurrence is an attractive concept. Here we investigated whether Nintedanib (BIBF 1120), a tyrosine kinase inhibitor (TKI) targeting the VEGF pathway approved for lung adenocarcinoma, and the dual anti-VEGF-A/Ang2 nanobody BI836880 have the potential to prevent BM formation. A mouse model of brain metastasis from lung adenocarcinoma was used in which tumor cells were injected intracardially. Metastases formation occurred inside and outside of the brain and was followed by MRI, IVIS, and immunohistochemistry. BM were reduced in volume and number by both Nintedanib and the dual anti-VEGF-A/Ang2 nanobody, which translated into improved survival. Both compounds were able to normalize cerebral blood vessels at the site of brain metastatic lesions. Extracranial metastases, however, were not reduced, and meningeal metastases only partially. Interestingly, unspecific control IgG also lead to brain vessel normalization and reduction of brain and meningeal metastases. This data indicates a brain-specific group effect of antiangiogenic compounds with respect to metastasis prevention, most likely by preventing an early angiogenic switch. Thus, Nintedanib and BI836880 are promising candidates for future BM preventive study concepts in lung adenocarcinoma patients.


Expression of transfected human Na+/H+ exchanger (NHE-1) in the the basolateral membrane of opossum kidney cells.
Some epithelial cells have Na+/H+ exchanger (NHE) activity in both apical and basolateral membranes. Amiloride-sensitive NHE-1 is generally identified in the basolateral membrane. The renal cell line, OK7a, targets amiloride-resistant NHE predominantly to the apical membrane. It is controversial whether the transfected NHE-1 is targeted preferentially to the basolateral membrane in OK7a cells, when human NHE-1 is chronically expressed under control of constitutively active promoters. We tried to identify the membranes in which the transfected human NHE-1 could be detected following acute expression in OK7a cells. We have always observed small Na(+)-dependent pH recovery in the basolateral membrane in OK7a cells. It is, however, controversial whether or not OK7a cells express NHE activity in the basolateral membrane. We also characterized Na(+)-dependent pH recovery in the basolateral membrane. It was not inhibited by [4,4'diisothiocyanatostilbene-2,2'-disulfonic acid] (DIDS), [4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid] (SITS), or contralateral amiloride. Li+ but not K+, chol+, or NMG+ could replace Na+. These results are consistent with the presence of the NHE in the basolateral membrane. NHE activities were predominant in the apical membrane and those in both membranes were resistant to amiloride analogs. After stable transfection with human NHE-1 in a vector utilizing the metallothionein promoter, overnight induction with Zn(2+)increased the NHE activity and its sensitivity to amiloride only in the basolateral membrane in OK7a cells. We conclude that the transfected human NHE-1 is exclusively targeted to the basolateral membrane of OK7a cells during acute induction.


Acute changes in N-terminal pro-brain natriuretic peptide induced by dobutamine stress echocardiography.
Aim of the study was to determine the effect of dobutamine stress echocardiography (DSE)-induced ischemia on circulating levels of N-terminal fragment of B-type natriuretic peptide (NT-pro-BNP). One hundred and twenty-eight patients underwent DSE for the evaluation of known or suspected coronary artery disease. NT-pro-BNP levels were measured before and 1h after completion of DSE. NT-pro-BNP levels were similar before and after DSE regardless of whether patients had (123+/-101.8 vs. 124.2+/-108.3, p=NS) or did not have inducible ischemia (96.5+/-70.5 vs. 100.5+/-71.1, p=NS). Patients with inducible myocardial ischemia had no different NT-pro-BNP levels compared to patients without inducible ischemia both before (123+/-101.8 vs. 96.5+/-70pg/ml, p=0.37) and after DSE (124.2+/-108.3 vs. 100.5+/-71.1pg/ml, p=0.55). Patients with severe inducible ischemia had significantly higher NT-pro-BNP levels compared to patients with mild or moderate inducible ischemia and patients without inducible ischemia, both before (208.5+/-125.5 vs. 96+/-78.9 vs. 96.5+/-70pg/ml, p=0.017 and p=0.025, respectively) and after DSE (212.5+/-138.1 vs. 94.8+/-81.1 vs. 100.5+/-71.1pg/ml, p=0.015 and p=0.023, respectively). NT-pro-BNP levels before DSE could be independently predicted by age (p<0.0001), presence of diabetes mellitus (p=0.002), and ejection fraction (p=0.005), but not DSE inducible ischemia. NT-pro-BNP is not affected by DSE-induced ischemia and cannot be used in clinical practice to improve diagnostic accuracy of DSE.


Update on treatment of rheumatoid arthritis.
To review current treatment of rheumatoid arthritis (RA), as well as recent advances. MEDLINE search from 1990 to 1998 for human studies using search terms "rheumatoid arthritis"; "cyclooxygenase inhibitors" combined with "anti-inflammatory agents, nonsteroidal"; "tumor necrosis factor" limited to "antagonists and inhibitors"; "isoxazoles." RA is a chronic inflammatory disease characterized by symmetrical joint involvement, usually of the small joints of the hands and feet. Although the hallmark of the disease is inflammation of joints, other organ systems--including the eyes, blood vessels, lungs, and cardiopulmonary system--may also be involved. Treatment of RA requires both drug and non-drug approaches. Current drug therapy consists of combinations of nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). Corticosteroids are also used either for short-term treatment during initiation of therapy, in bursts during acute disease flares, or chronically in low doses. A number of promising new agents are in development. NSAIDs with preferential inhibition of cyclooxygenase II may offer a better safety profile than existing agents. Leflunomide and biological agents such as etanercept may provide benefit for patients who fail to achieve adequate response from conventional therapy. Traditional approaches to treatment of RA include NSAIDs combined with DMARDs. New agents just reaching the market represent important advances and have the potential to make a positive impact on treatment of RA.


Vaccination of stage IV patients with allogeneic IL-4- or IL-2-gene-transduced melanoma cells generates functional antibodies against vaccinating and autologous melanoma cells.
The antibody (Ab) response to allogeneic Me14932 and autologous melanoma cells was analyzed in 13 Stage IV (AJCC) melanoma patients immunized with Me14932 cells transduced with the IL-4 (Me14932/IL-4) ( n=10) or IL-2 (Me14932/IL-2) ( n=3) gene. No Ab response was observed before the 4th vaccination. Among 8 patients that received four vaccinations, 3/5 patients vaccinated with Me14932/IL-4 cells developed Ab (IgG and/or IgM) to Me14932 ( n=3) and to autologous ( n=2) melanoma cells, and 2/3 patients vaccinated with Me14932/IL-2 cells developed Ab (IgG) to Me14932, but not to autologous melanoma cells. Further, among these 5 responding patients, circulating Ab against the HLA-A3 allele, expressed only on vaccinating cells, were identified in the immune sera of 4 patients immunized with Me14932/IL-4 ( n=2) or Me14932/IL-2 ( n=2) cells. These sera mediated antibody-dependent cell cytotoxicity (ADCC) of Me14932 cells, and a direct correlation ( r=0.85; P=0.03) between intensity of staining (IgG) and extent of lysis was found. Immune serum of one of these patients also induced ADCC of autologous melanoma cells, and serum from another patient mediated complement cytotoxicity of Me14932, but not of autologous melanoma cells. Thus, Abs against vaccinating and autologous melanoma cells were generated in 62% of patients after four vaccinations with cytokine-transduced melanoma cells. These findings demonstrate that the identification and titration of alloreactive Ab helps to monitor the extent of immunization against cellular vaccines, while the induction of Ab reactive to antigens shared between vaccinating and autologous melanoma cells may contribute to their therapeutic efficacy.


Proteolysis of a histone acetyl reader, ATAD2, induces chemoresistance of cancer cells under severe hypoxia by inhibiting cell cycle progression in S phase.
Cancer cells acquire chemoresistance in hypoxic regions of solid tumors, which is suggested to be at least partly due to reduction of their proliferative activity. However, molecular mechanisms behind it have not been fully elucidated. Here, we revealed the importance of active proteolysis of a histone acetylation reader, ATPase family AAA domain containing 2 (ATAD2), under hypoxia. We found that inactivation of an O2/Fe2+/α-ketoglutarate-dependent dioxygenase triggered ATAD2 proteolysis by the proteasome system upon severe hypoxia in a hypoxia-inducible factors (HIFs)-independent manner. Consistently, ATAD2 expression levels were markedly lower in perinecrotic hypoxic regions in both xenografted and clinical tumor tissues. The ATAD2 proteolysis was accompanied by a decrease in the amount of acetylated histone H3 lysine 27 and inhibited cell cycle progression from the early to late S phase under severe hypoxia. The retardation of S phase progression induced chemoresistance, which was blocked by overexpression of ATAD2. Together, these results indicate that ATAD2 proteolysis upon severe hypoxia induces chemoresistance of cancer cells through heterochromatinization and the subsequent retardation of S phase progression; therefore, inhibition of ATAD2 proteolysis is expected to be a strategy to overcome chemoresistance of hypoxic tumor cells.


The seminal microbiome in health and disease.
Owing to the fact that there are more microbial than human cells in our body and that humans contain more microbial than human genes, the microbiome has huge potential to influence human physiology, both in health and in disease. The use of next-generation sequencing technologies has helped to elucidate functional, quantitative and mechanistic aspects of the complex microorganism-host interactions that underlie human physiology and pathophysiology. The microbiome of semen is a field of increasing scientific interest, although this microbial niche is currently understudied compared with other areas of microbiome research. However, emerging evidence is beginning to indicate that the seminal microbiome has important implications for the reproductive health of men, the health of the couple and even the health of offspring, owing to transfer of microorganisms to the partner and offspring. As this field expands, further carefully designed and well-powered studies are required to unravel the true nature and role of the seminal microbiome.


Evaluation of the effect of the Momentum project on family planning outcomes among first-time mothers aged 15-24 years in Kinshasa, DRC.
This article presents the effect of Momentum, a nursing student-led community-based service delivery project, on postpartum family planning (FP) outcomes among first-time mothers in Kinshasa, Democratic Republic of the Congo. We employed a quasi-experimental design, with three intervention and three comparison health zones (HZ). Data were collected through interviewer-administered questionnaires in 2018 and 2020. The sample consisted of 1927 nulliparous women aged 15-24 years who were 6 months pregnant at baseline. Random effects and treatment effects models were used to assess the effect of Momentum on 14 postpartum FP outcomes. The intervention group was associated with a unit increase of 0.6 (95% confidence interval [CI]: 0.4, 0.8)) in contraceptive knowledge and personal agency (95% CI: 0.3, 0.9), a unit decrease of 0.9 (95% CI: -1.2, -0.5) in the number of FP myths/misconceptions endorsed, and percentage point increases of 23.4 (95% CI: 0.2, 0.3) in FP discussion with a health worker, 13.0 (95% CI: 0.1, 0.2) in obtaining a contraceptive method within 6 weeks of delivery, and 13.3 (95% CI: 0.1, 0.2) in modern contraceptive use within 12 months of delivery. Intervention effects included percentage point increases of 5.4 (95% CI: 0.0, 0.1) in partner discussion and 15.4 (95% CI: 0.1, 0.2) in perceived community support for postpartum FP use. The level of exposure to Momentum was significantly associated with all behavioral outcomes. The study demonstrated the effect of Momentum on increased postpartum FP-related knowledge, perceived norms, personal agency, partner discussion, and modern contraceptive use. Community-based service delivery by nursing students can potentially lead to improved postpartum FP outcomes among urban adolescent and young first-time mothers in other provinces of the Democratic Republic of the Congo and other African countries.


Synaptic physiology of central CRH system.
Corticotropin-Releasing Hormone (CRH) or Corticotropin-Releasing Factor (CRF) and its family of related naturally occurring endogenous peptides and receptors are becoming recognized for their actions within central (CNS) and peripheral (PNS) nervous systems. It should be recognized that the term 'CRH' has been displaced by 'CRF' [Guillemin, R., 2005. Hypothalamic hormones a.k.a. hypothalamic releasing factors. J. Endocrinol. 184, 11-28]. However, to maintain uniformity among contributions to this special issue we have used the original term, CRH. The term 'CRF' has been associated recently with CRH receptors and designated with subscripts by the IUPHAR nomenclature committee [Hauger, R.L., Grigoriadis, D.E., Dallman, M.F., Plotsky, P.M., Vale, W.W., Dautzenberg, F.M., 2003. International Union of Pharmacology. XXXVI. Corticotrophin-releasing factor and their ligands. Pharmacol. Rev. 55, 21-26] to denote the type and subtype of receptors activated or antagonized by CRH ligands. CRH, as a hormone, has long been identified as the regulator of basal and stress-induced ACTH release within the hypothalamo-pituitary-adrenal axis (HPA axis). But the concept, that CRH and its related endogenous peptides and receptor ligands have non-HPA axis actions to regulate CNS synaptic transmission outside the HPA axis, is just beginning to be recognized and identified [Orozco-Cabal, L., Pollandt, S., Liu, J., Shinnick-Gallagher, P., Gallagher, J.P., 2006a. Regulation of Synaptic Transmission by CRF Receptors. Rev. Neurosci. 17, 279-307; Orozco-Cabal, L., Pollandt, S., Liu, J., Vergara, L., Shinnick-Gallagher, P., Gallagher, J.P., 2006b. A novel rat medial prefrontal cortical slice preparation to investigate synaptic transmission from amygdala to layer V prelimbic pyramidal neurons. J. Neurosci. Methods 151, 148-158] is especially noteworthy since this synapse has become a prime focus for a variety of mental diseases, e.g. schizophrenia [Fischbach, G.D., 2007. NRG1 and synaptic function in the CNS. Neuron 54, 497-497], and neurological disorders, e.g., Alzheimer's disease [Bell, K.F., Cuello, C.A., 2006. Altered synaptic function in Alzheimer's disease. Eur. J. Pharmacol. 545, 11-21]. We suggest that "The Stressed Synapse" has been overlooked [c.f., Kim, J.J., Diamond, D.M. 2002. The stressed hippocampus, synaptic plasticity and lost memories. Nat. Rev., Neurosci. 3, 453-462; Radley, J.J., Morrison, J.H., 2005. Repeated stress and structural plasticity in the brain. Ageing Res. Rev. 4, 271-287] as a major contributor to many CNS disorders. We present data demonstrating CRH neuroregulatory and neuromodulatory actions at three limbic synapses, the basolateral amygdala to central amygdala synapse; the basolateral amygdala to medial prefrontal cortex synapse, and the lateral septum mediolateral nucleus synapse. A novel stress circuit is presented involving these three synapses. We suggest that CRH ligands and their receptors are significant etiological factors that need to be considered in the pharmacotherapy of mental diseases associated with CNS synaptic transmission.


Ball-bearing keratometry.
We obtained steel test balls for keratometer calibration at nominal cost by using a selected set of steel ball bearings, readily available for nonoptical purposes. The set of keratometer tests balls each have an accuracy of greater than one part in 1,000.


Manipulating the morphology of colloidal particles via ion beam irradiation: A route to anisotropic shaping.
Ion beam irradiation of spherical colloidal particles is a viable route to induce particle deformation, especially to get anisotropic shapes. Even though less common in comparison with dry etching techniques, different types of morphological changes can be attained depending on the process parameters (angle of incidence, energy, fluence of the ion beam, type of ion, temperature) and on particle material and initial particle arrangement (crystalline or disordered, made up of isolated or closely-packed particles). The technique can be harnessed to get anisotropic deformation of spherical colloidal particles into an ellipsoidal shape, but also to tailor the interstices between closely-packed colloidal particles, to get particle necking and coalescence as well as particle rearrangement. As such, particle deformation based on ion irradiation can find diverse applications from synthesis of ellipsoidal particles to modified templates for colloidal lithography. In this review, we examine in detail the principles and models of colloidal particle shaping via ion beam irradiation, the influence of process parameters on particle morphology and the applications of irradiated particles.


The Acetic Acid Tolerance Response induces cross-protection to salt stress in Salmonella typhimurium.
Salmonella typhimurium induces an Acid Tolerance Response (ATR) upon exposure to mildly acidic conditions in order to protect itself against severe acid shock. This response can also induce cross-protection to other stresses such as heat and salt. We investigated whether both the acetic acid induced and lactic acid induced ATR in S. typhimurium provided cross-protection to a salt stress at 20 degrees C. Acid-adapted cells were challenged with both a sodium chloride (NaCl) and potassium chloride (KCl) shock and their ability to survive ascertained. Acetic acid adaptation provided cells with protection against both NaCl and KCl stress. However, lactic acid adaptation did not protect against either osmotic stressor and rendered cells hypersensitive to NaCl. These results have implications for the food industry where hurdle technology means multiple sub-lethal stresses such as mild pH and low salt are commonly used in the preservation of products.


That tool is rubbish!…or is it?
Digital forensic practitioners often utilise a range of tools throughout their casework in order to access, identify and analyse relevant data, making them a vital part of conducting thorough, efficient and accurate digital examinations of device content and datasets. Whilst their importance cannot be understated, there is also no guarantee that their functionality is free from error, where similarly, no practitioner can 100% assure that their performance is flawless. Should an error occur during an investigation, assuming that it has been identified, then determining the cause of it is important for the purposes of ensuring quality control in both the immediate investigation and for longer-term practice improvements. Perhaps anecdotally, a starting position in any postmortem review of an error may be to suspect that any tools used may be at fault, where recent narratives and initiatives have enforced the need to evaluate all tools prior to them being used in any live investigation. Yet, in addition, an error may occur as a result of a practitioner's investigative conduct. This work discusses the concept of 'fault-attribution', focusing on the roles of the forensic tool and practitioner, and proposes a series of principles for determining responsibility for an investigative error.


Alterations in contrast medium-induced coronary reactive hyperemia after bepridil in patients with coronary artery disease.
The acute effects of an intravenous infusion of bepridil (BEP) (4 mg . kg-1) on left ventricular (LV) hemodynamics, coronary sinus blood flow (CSBF), and myocardial metabolism were studied in eight patients with coronary artery disease. In contrast with data previously reported with calcium channel blockers, BEP induced an elevation in LV end-diastolic pressure from 12.0 +/- 7.1 to 20.1 +/- 7.2 mm Hg (mean +/- SD, p less than 0.001) and a fall in LV dp/dt max from 1339 +/- 302 to 1177 +/- 251 mm Hg . sec-1 (p less than 0.01). This significant alteration in LV function is likely to be explained by the lack of effect on heart rate and aortic pressure observed after an acute intravenous infusion of BEP. Myocardial oxygen consumption (MVO2) increased from 448 +/- 272 to 498 +/- 273 mumol . min-1/100 g LV (p less than 0.05) as did CSBF from 79.5 +/- 42.7 to 92.1 +/- 45.1 ml X min-1/100 g LV (p less than 0.01). Lactate extraction fell from 0.33 +/- 0.17 to 0.15 +/- 0.17 (p less than 0.05). A contrast medium-induced coronary reactive hyperemia (HPR) evidenced an increased hyperemic volume from 9.5 +/- 3.6 to 12.1 +/- 4.5 ml/100 g LV (p less than 0.01) and HPR duration from 23.3 +/- 6.9 to 32.3 +/- 15.4 sec (p less than 0.05) after BEP. However, the peak/resting CSBF ratio was blunted after BEP from 1.74 +/- 0.18 to 1.61 +/- 0.12 (p less than 0.05), evidencing a net effect of BEP on HPR.(ABSTRACT TRUNCATED AT 250 WORDS)


Oxidation product(s) in acetaldehyde reacts with NAD(P)H and interferes with assay of alcohol dehydrogenase.
A decrease in absorbance at 340 nm, at rates similar to those obtained with alcohol dehydrogenases in routine assays, occurred when NADH or NADPH was mixed with acetaldehyde that had been exposed to air for various durations. NAD(P)H was apparently oxidized by interfering substance(s) present in acetaldehyde. Reagent-grade acetaldehyde from newly opened bottles as well as acetaldehyde redistilled under strictly O2-free conditions contained minimal amounts of NAD(P)H-reacting substance(s). Redistillation under poor anaerobic conditions or in air increased the amount of NAD(P)H-reacting substance(s) in redistilled acetaldehyde. NADPH reacted at a higher rate than NADH with the interfering substance(s) in Tris-Cl buffer at pH 7.5. Also, the reaction was faster in Tris buffer than in phosphate buffer at pH 7.5. The NAD(P)H-oxidizing reaction may not be apparent when the nominal concentration of acetaldehyde used was below 5 mM, but the measured ethanol dehydrogenase activity could be significantly lower with acetaldehyde containing a measurable level of interfering substance(s). This study suggests that acetaldehyde is most easily tested with NADPH for the presence of a significant level of interfering substance(s) and that redistillation, if necessary, must be performed under strictly O2-free conditions.


Ambulatory surgery centers: A 2012 to 2018 analysis on growth in number of centers, utilization, Medicare services, and Medicare reimbursements.
Given declining reimbursements and potential financial conflicts of interest in ownership, it is important to continually assess ambulatory surgery center role and growth. The objective of this study is to evaluate scope of practice, number of patients served, number of procedures performed, and revenue of ambulatory surgery centers within a Medicare fee-for-service population. This retrospective study includes data from Medicare Part B: Provider Utilization and Payment Datafiles (2012-2018). In addition to total number and geographic distribution, sums and medians were gathered for Medicare reimbursements, services performed, number of patients, and unique current procedural terminology codes used. The number of Medicare fee-for-service-serving ambulatory surgery centers grew 7.0% from 4,886 to 5,227 between 2012 and 2018. A total of 8,169,288 Medicare fee-for-service services were performed on 3,910,434 patients in 2018, an increase of 10.8% and 6.5% since 2012, respectively. At the median, each ambulatory surgery center performed 1,050 services in 2018, which was slightly less than in 2012 (median: 1,094). Ambulatory surgery centers collected $5.1 billion in payments in 2018, compared to $3.6 billion in 2012 (29.1% inflation-adjusted growth). Total inflation-adjusted allowed Medicare fee-for-service payments have increased 29.1% between 2012 and 2018, despite just 7% growth in number of ambulatory surgery centers and 10.8% increase in total number of services. The 16.5% increase in inflation-adjusted revenue generated per service may indicate that the increased use of complex procedures with higher reimbursement, previously only performed in an inpatient setting, are now offered more readily in ambulatory surgery centers.


ISAR Consensus Guidelines on Add-Ons Treatment in In vitro Fertilization.
What are the good practices for the use of ADD-ON Treatments in IVF cycles in INDIA? Add on treatments in IVF are procedures and technologies which are offered to patients in hope of improving the success rates. A lot of add on treatments exist; most of them have limited evidence and data for the Indian patient population is miniscule. These interventions may have limited effects, so it is imperative that any new technology that is offered is evaluated properly and has enough evidence to suggest that it is safe and effective. This is the report of a 2-day consensus meeting where two moderators were assigned to a group of experts to collate information on Add on treatments in IVF in INDIA. This meeting utilised surveys, available scientific evidence and personal laboratory experience into various presentations by experts on pre-decided specific topics. Expert professionals from ISAR representing clinical and embryology fields. The report is divided in various components including the health of the Offspring, the various ADD ons available to an ART center, consensus points for each technology & qualifications and trainings for embryologists, the report and recommendations of the expert panel reflect the discussion on each of the topics and try to lay down good practice points for labs to follow. The recommendations are solely based on expert opinion. Future availability of data may warrant an update of the same. These guidelines can help labs across the country to standardise their ART services and improve clinical outcomes, it will also motivate clinics to collect data and report the use of Add ons to the national registry. The consensus meeting and writing of the paper was supported by funds from CooperSurgical India.


Effects of dietary protein and stage of lactation on the haematology and erythrocyte enzymes activities of high-producing dairy cattle.
Blood samples were collected monthly over a nine-month period from 19 high-producing Holstein-Friesian dairy cows. Dry cows on the lowest (13 per cent) protein ration had the highest mean values for packed cell volume (PCV), haemoglobin (Hb) and red blood cells (RBC). Among the lactating cows, the group on the 13 per cent protein diet had the highest mean PCV, Hb and RBC values. Other constituents were not affected significantly by dietary protein levels. Packed cell volume, RBC, Hb, serum iron (SI), iron binding capacity (IBC) and serum albumin concentrations decreased early in lactation and rose to pre-lactation levels by mid-lactation. PCV and Hb concentrations remained low for periods up to four months. RBC count was lowest in the second month while albumin concentration was lowest in the first month and remained low up to the second month. IBC was lowest in the first month of lactation while SI concentrations were lowest in the third month. There were no significant variations in the activities of erythrocyte glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD) and reduced glutathione (GSH). The 13 per cent protein ration had no anaemia-inducing effect on the cows.


Remarkable Near-Infrared Electrochromism in Tungsten Oxide Driven by Interlayer Water-Induced Battery-to-Pseudocapacitor Transition.
Near-infrared (NIR) electrochromism is of academic and technological interest for a variety of applications in advanced solar heat regulation, photodynamic therapy, optical telecommunications, and military camouflage. However, inorganic materials with outstanding NIR modulation capability are quite few. Herein, we propose a promising strategy for achieving strong NIR electrochromism in tungsten oxide that is closely related to its electrochemical transformation from battery-type behavior to pseudocapacitance, induced by introducing an interlayer space with water molecules within tungsten oxide. Further evidence demonstrates that the interlayer water molecules significantly reduced the energy barrier to ion diffusion and increased the ion flux in tungsten oxide. As a result, compared with anhydrous WO3, the as-synthesized WO3·2H2O nanoplates exhibited remarkably improved NIR electrochromic properties, including a large transmittance modulation (90.4%), high coloration efficiency (322.6 cm2 C-1), and high cyclic stability (maintaining 93.7% after 500 cycles), which were comparable to those of the best reported NIR electrochromic materials. Moreover, the application of the WO3·2H2O nanoplate-based electrochromic device resulted in a temperature difference of 11.9 °C, indicating good solar thermal regulation ability.


Molecular anatomy of Tupaia (tree shrew) adenovirus genome; evolution of viral genes and viral phylogeny.
Adenoviruses are globally spread and infect species in all five taxons of vertebrates. Outstanding attention is focused on adenoviruses because of their transformation potential, their possible usability as vectors in gene therapy and their applicability in studies dealing with, e.g. cell cycle control, DNA replication, transcription, splicing, virus-host interactions, apoptosis, and viral evolution. The accumulation of genetic data provides the basis for the increase of our knowledge about adenoviruses. The Tupaia adenovirus (TAV) infects members of the genus Tupaiidae that are frequently used as laboratory animals in behavior research dealing with questions about biological and molecular processes of stress in mammals, in neurobiological and physiological studies, and as model organisms for human hepatitis B and C virus infections. In the present study the TAV genome underwent an extensive analysis including determination of codon usage, CG depletion, gene content, gene arrangement, potential splice sites, and phylogeny. The TAV genome has a length of 33,501 bp with a G+C content of 49.96%. The genome termini show a strong CG depletion that could be due to methylation of these genome regions during the viral replication cycle. The analysis of the coding capacity of the complete TAV genome resulted in the identification of 109 open reading frames (ORFs), of which 38 were predicted to be real viral genes. TAV was classified within the genus Mastadenovirus characterized by typical gene content, arrangement, and homology values of 29 conserved ORFs. Phylogenetic trees show that TAV is part of a separate evolutionary lineage and no mastadenovirus species can be considered as the most related. In contrast to other mastadenoviruses a direct ancestor of TAV captured a DUT gene from its mammalian host, presumably controlling local dUTP levels during replication and enhance viral replication in non-dividing host tissues. Furthermore, TAV possesses a second DNA-binding protein gene, that is likely to play a role in the determination of the host range. In view of these data it is conceivable that TAV underwent evolutionary adaptations to its biological environment resulting in the formation of special genomic components that provided TAV with the ability to expand its host range during viral evolution.


New specific marker of cytochrome P450 1A2 activity.
Various methods were proposed for phenotyping of patients by activity of cytochrome P450 1A2, each has some advantages and disadvantages. However, no reference parameters were developed for measuring CYP1A2 activity that could be used as a unified standard for phenotyping of patients. We propose a mathematic model of caffeine metabolism allowing calculation of rate constants for the formation of its primary metabolites. First-order rate constant of paraxanthine formation was tested as a new specific marker of isoenzyme 1A2 in healthy volunteers.


Atlantoaxial dislocation due to os odontoideum in patients with Down's syndrome: literature review and case reports.
To clarify etiology, clinical features, and diagnostic and treatment options of atlantoaxial dislocation (AAD) due to os odontoideum (OsO) in patients with Down's syndrome (DS). We described and analyzed three clinical cases of AAD due to OsO in DS patients and reviewed descriptions of similar cases in the scientific sources. According to literature review, more than 80% of DS patients with odontoid ossicles had atlantoaxial instability (AAI). AAI in DS patients with OsO is more often manifested in childhood and adolescence, rarely in adults when ligament relaxation is reduced. Some patients had acute clinical manifestation after a minor trauma without any precursors; in some of the cases, neurological deterioration increased during several years. We found that the earlier surgical treatment of AAD due to OsO in DS patients carries the higher recovery potential. Most patients with DS and OsO had AAI. The method of appropriate treatment in such cases is a posterior screw fixation. Preoperative halo traction and posterior fusion have proved to be a very useful tool in the treatment of AAD due to OsO in DS patients. Even if irreducibility of the AAD established preoperatively, it should not be an absolute indication for anterior decompression. In such cases, an attempt to reduce the AAD should be made under general anesthesia during posterior fixation.


Using enhanced text to facilitate recognition of drug names: evidence from two experimental studies.
Two studies examined the effects of enhanced text on immediate recognition of drug names. Study 1 sampled 102 college students using a between-subjects design, while Study 2 sampled 11 practicing pharmacists and technicians using a within-subjects Latin square design. Both studies utilized a computer-based sequential recognition task where a prime word was shown with various text enhancements, followed by a mask and then a target word. Participants decided whether the target word was the same as the prime word. Stimuli were organized so that 120 trials were matches and 120 trials were mismatches, randomly sequenced for each participant. Results showed an effect of orthographic similarity, where high-similarity name mismatches were missed more often. This effect was independent of the type of text enhancement used and response bias. Case-based enhancements also increased errors of commission (false alarms) significantly. Discussion includes the practical relevance of the data and future directions for research.


Pediatric intracranial aneurysms: an institutional experience.
Intracranial aneurysms are extremely uncommon in the pediatric population. Their epidemiology is poorly understood, and certain features make them unique. In our study we analyzed pediatric intracranial aneurysm patients to gain an insight into the epidemiology, clinicoradiological profile and outcome. Out of 36 children (< or =18 years of age; male:female ratio = 1.076:1; mean age 13.19 +/- 3.72 years, age range 5-18 years) presenting with subarachnoid hemorrhage (SAH; n = 33; 91.67%) and mass effect (n = 3; 8.33%), 27 who were positive on digital subtraction angiography and treated for intracranial aneurysms between January 1991 and February 2007 were included in this study. At presentation, the majority (n = 21) of the pediatric intracranial patients showed a good grade, and 23 (85.18%) presented with SAH. Sudden severe headache (n = 19; 70.37%) and loss of consciousness (n = 14; 51.85%) were the most common symptoms, and meningeal signs (n = 18; 66.66%) most commonly elicitable. There were 7 patients with giant aneurysms and 8 patients with posterior circulation aneurysms. Internal carotid artery (ICA) bifurcations (n = 6; 18.18%) followed by middle cerebral artery (MCA) bifurcations (n = 4; 12.12%) were the most common sites. At a mean follow-up of 18.67 +/- 10.85 months (range 1-42 months), there were 21 (77.77%) patients with favorable outcome and 3 patients died. Intracranial aneurysms in children commonly present with SAH; there is a male predominance, and ICA bifurcations followed by MCA bifurcations are the most common sites. The incidence of posterior circulation aneurysms and giant aneurysms is higher as compared to adults. The pediatric patients present with better grades and have better overall surgical results.


Dielectric spectroscopy: a technique for the determination of water coordination within ionic liquids.
The presence of water can have a significant influence upon both the physical and dielectric properties of ionic liquids and consequently their ability to interact with microwaves. Herein we show that complex permittivity initially decreases as low concentrations of water are added to the system, the continued addition of water gives rise to an inversion in this trend. We propose that this minimum point may be used to identify water dimer formation.


Localization and identification of parapharyngeal metastases from differentiated thyroid carcinoma by 131I-SPECT/CT.
Parapharyngeal metastasis is a rare event in differentiated thyroid carcinoma (DTC). The (131) I-single photon emission CT (SPECT)/CT allows better localization and definition for metastases in DTC. The aim of this study was to assess the value of (131) I-SPECT/CT for the diagnosis of parapharyngeal metastasis in patients with DTC. Consecutive patients with DTC (n = 561) treated with (131) I for the ablation of remnant or treatment of metastases were enrolled. A (131) I-SPECT/CT was performed when there were abnormal findings indicative of parapharyngeal metastasis on (131) I-whole-body scan (WBS). A total of 15 lesions were found to be parapharyngeal metastasis in 14 of 561 patients with DTC after the use of (131) I-SPECT/CT. The incidence rate of parapharyngeal metastasis was about 2.5% in DTC. Of the 15 lesions, only 5 lesions were CT-positive. The remaining 10 lesions were either ignored or indeterminate by the CT alone. The (131) I-SPECT/CT can identify parapharyngeal metastasis at an early stage. Parapharyngeal metastasis in DTC is relatively frequent after the use of (131) I-SPECT/CT.


Rapamycin: an anti-cancer immunosuppressant?
Rapamycin and its derivatives are promising therapeutic agents with both immunosuppressant and anti-tumor properties. These rapamycin actions are mediated through the specific inhibition of the mTOR protein kinase. mTOR serves as part of an evolutionarily conserved signaling pathway that controls the cell cycle in response to changing nutrient levels. The mTOR signaling network contains a number of tumor suppressor genes including PTEN, LKB1, TSC1, and TSC2, and a number of proto-oncogenes including PI3K, Akt, and eIF4E, and mTOR signaling is constitutively activated in many tumor types. These observations point to mTOR as an ideal target for anti-cancer agents and suggest that rapamycin is such an agent. In fact, early preclinical and clinical studies indicate that rapamycin derivatives have efficacy as anti-tumor agents both alone, and when combined with other modes of therapy. Rapamycin appears to inhibit tumor growth by halting tumor cell proliferation, inducing tumor cell apoptosis, and suppressing tumor angiogenesis. Rapamycin immunosuppressant actions result from the inhibition of T and B cell proliferation through the same mechanisms that rapamycin blocks cancer cell proliferation. Therefore, one might think that rapamycin-induced immunosuppression would be detrimental to the use of rapamycin as an anti-cancer agent. To the contrary, rapamycin decreases the frequency of tumor formation that occurs in organ transplant experiments when combined with the widely used immunosuppressant cyclosporine compared with the tumor incidence observed when cyclosporine is used alone. The available evidence indicates that with respect to tumor growth, rapamycin anti-cancer activities are dominant over rapamycin immunosuppressant effects.


Wettability Analysis of Water on Metal/Semiconductor Phases Selectively Structured with Femtosecond Laser-Induced Periodic Surface Structures.
Femtosecond (fs) laser-induced periodic surface structures (LIPSS) were selectively generated on the surface of an Ag-Si alloy consisting of a metallic and a semiconducting phase. For this purpose, the alloy was irradiated with linearly polarized fs-laser pulses (τ = 300 fs, λ = 1025 nm, frep = 100 kHz) using a laser peak fluence F = 0.30 J/cm2. Due to the different light absorption behaviors of the semiconductor (Si) and the metal (Ag) phases that result in different ablation thresholds of the respective phases, pronounced LIPSS with a period of Λ ≈ 950 nm and a modulation depth of h ≈ 220 nm were generated solely on the Si phase. The alloy surface was characterized by scanning electron microscopy, optical microscopy, white-light interference microscopy, and atomic force microscopy before and after laser irradiation. The chemical analysis was carried out by energy-dispersive X-ray spectroscopy, revealing surface oxidation of the Si phase and no laser-induced chemical modification of the Ag phase. The surface wettability of the alloy was evaluated with distilled water and compared to those of the single constituents of the composites. After fs-laser irradiation, the surface is characterized by a reduced hydrophilic water contact angle. Furthermore, the alloy selectively structured with LIPSS revealed a droplet shape change due to the distinctly different contact angles on the Si (θ = 5°) and Ag (θ = 74°) phases. This phenomenon was evaluated and discussed by local contact angle analyses using a confocal laser scanning microscope and Rhodamine B dye. In addition, it was shown that the shape change due to different contact angles of the components allowed a targeted droplet movement on a macroscopic material boundary (Ag/Si) of the alloy. Selectively structured metal/semiconductor surfaces might be of particular interest for microfluidic devices with a directional droplet movement and for the fundamental research of wettability.


Cerebral representations of space and time.
A link between perception of time and spatial change is particularly revealed in dynamic conditions. By fMRI, we identified regional segregation as well as overlap in activations related to spatial and temporal processing. Using spatial and temporal anticipation concerning movements of a ball provided a balanced paradigm for contrasting spatial and temporal conditions. In addition, momentary judgments were assessed. Subjects watched a monitor-display with a moving ball that repeatedly disappeared. Ordered in 4 conditions, they indicated either where or when the ball would hit the screen bottom, where it actually disappeared or what its speed was. Analysis with SPM showed posterior parietal activations related to both spatial- and temporal predictions. After directly contrasting these two conditions, parietal activations remained robust in spatial prediction but virtually disappeared in temporal prediction, while additional left cerebellar-right prefrontal and pre-SMA activations in temporal prediction remained unchanged. Speed contrasted to the location of disappearance showed similar parietal decrease with maintained cerebellar-prefrontal activations, but also increased caudate activation. From these results we inferred that parietal-based spatial information was a prerequisite for temporal processing, while prefrontal-cerebellar activations subsequently reflected working memory and feedforward processing for the assessment of differences between past and future spatial states. We propose that a temporal component was extracted from speed, i.e. approximated momentary time, which demarcated minimal intervals of spatial change (defined by neuronal processing time). The caudate association with such interval demarcation provided an argument to integrate concepts of space-referenced time processing and a clock-like processing model.


Resistin forms a network with inflammatory cytokines and is associated with prognosis in major burns.
In current intensive care treatment, some patients with severe burns cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients. This was a single-center, retrospective, observational study. Patients' blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured. Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801. In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.


A novel multifunctional mitochondrion-targeting NIR fluorophore probe inhibits tumour proliferation and metastasis through the PPARγ/ROS/β-catenin pathway.
Recent advancements in tumour-targeted therapies and immunotherapy offer hope to patients with various malignancies. However, the uncontrolled growth and metastatic infiltration of malignant tumours remain a huge therapeutic challenge. Therefore, this study aimed to develop an integrated multifunctional diagnostic and treatment reagent IR-251 that can not only be used for tumour imaging but also to inhibit tumour growth and metastasis. Besides, our results showed that IR-251 targeted and damaged the mitochondria in cancer cells via organic anion-transporting polypeptides. Mechanistically, IR-251 induced ROS overproduction by inhibiting PPARγ and then inhibiting the β-catenin signalling pathway and downstream protein molecules related to the cell cycle and metastasis. Moreover, the excellent anti-tumour proliferation and metastasis ability of IR-251 were verified in vitro/in vivo. And histochemistry staining revealed that IR-251 inhibited tumour proliferation and metastasis, which showed no significant side effect. In conclusion, this novel, multifunctional, mitochondria-targeting near-infrared fluorophore probe IR-251 has great potential in achieving accurate tumour imaging and inhibiting tumour proliferation and metastasis, and the underlying mechanism of action of IR-251 is mainly via the PPARγ/ROS/β-catenin pathway.


Catecholamine and 5-hydroxytryptamine synthesis and metabolism following intracerebroventricular injection of dibutyryl cyclic AMP.
Two to seven days after bilateral implantation of polyethylene tubings into the lateral ventricles rats were injected intracerebroventricularly with dibutyryl cAMP or dibutyryl cGMP. The accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhyrazine HCl, served as a measure of catecholamine and 5-hydroxytryptamine synthesis in vivo. A dose of 100 microgram dibutyryl cAMP per rat but not dibutyryl cGMP increased the accumulation of dopa in all brain regions by 70 to 130%. Both nucleotides stimulated the formation of 5-hydroxytryptophan in the dopamine-rich part of the limbic system and diencephalon and in addition dibutyryl cAMP increased 5-hydroxytryptophan in C. striatum and cerebellum. Dibutyryl cAMP (25-200 microgram per rat) did not change the dopamine levels in the dopamine-rich parts of the brain but decreased the noradrenaline level of the C. striatum in a dose-dependent manner. The same doses of dibutyryl cAMP elevated the 5-hydroxytryptamine level in brain stem and the level of 5-hydroxyindole acetic acid in diencephalon and the limbic system. The disappearance of noradrenaline but not of dopamine after inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine methylester HCl was accelerated in most brain regions. The data are compatible with the view that dibutyryl cAMP stimulates tyrosine and tryptophan hydroxylase directly. In addition, dibutyryl cAMP appears to enhance the utilization of noradrenaline but not that of dopamine. The increased utilization of 5-hydroxytryptamine may be restricted to the diencephalon and the limbic system.


[Comparative analysis of the effects of alcoholic drinks of different qualities (author's transl)].
The authors compared the effects of alcoholic drinks rich in fusel oil with the effects of diluted pure alcohol of the same quantity on 19 clinically healthy university students. The investigations utilized EEG and physiopsychic testing methods. The clinical symptoms were observed both under the effect of drinks and in a crapulous state ("hang-over"). It was found that alcoholic drinks rich in fusel oil can produce a more deviating EEG curve, an increased worsening of physiopsychic performance and of clinical and subjective symptoms. The necessity of regular quality control of alcoholic beverages is pointed out.


Prognostic implications of left atrial dilation evaluated by echocardiographic volume in patients with normal left atrial antero-posterior dimensions.
The purpose of this study was to clarify the clinical characteristics and prognostic implications of left atrial (LA) dilation evaluated echocardiographic volume in patients with normal LA dimension (LAD). A total of 140 consecutive patients (81 men, mean age: 57 ± 18 years) with normal LAD (<39 mm for women and <41 mm for men) who underwent conventional echocardiography and tissue Doppler imaging were enrolled. LA volume (LAV) ≥29 ml/m(2) was defined as abnormal LAV. Hospitalization for heart failure (HF) and cardiac death were defined as cardiac events. Eighty-seven (62%) of the patients had LA dilation, defined as a normal LAD but an abnormal LAV. Patients with LA dilation were significantly older and had a significantly higher left ventricular (LV) mass index (LVMI) and incidences of hypertension and HF than did patients with both normal LAD and normal LAV. Logistic regression analysis revealed that increased LVMI was an independent (p < 0.01) determinant of LA dilatation. During a follow-up period of 16 ± 10 months, ten patients had cardiac events. Patients with cardiac events had a higher incidence of LA dilation than those without cardiac events (100 vs. 59%, p < 0.05). A Kaplan-Meier survival curve showed that patients with LA dilation had a significantly lower survival rate than those with both normal LAD and normal LAV (log rank 6.1, p = 0.014). LV hypertrophy is an independent determinant of LA dilation in patients with normal LAD. Assessment of LA morphology using LAV can contribute to risk stratification in patients with normal LAD.


Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.
To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. After three months, HEs area was reduced to 52.9 ± 4.21% (P < 0.001) in the triamcinolone group, 63.6 ± 6.08% (P = 0.002) in the dexamethasone implant group, and 85.2 ± 5.07% (P = 0.198) in the bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P < 0.001) and at two months in the dexamethasone implant group (70.1 ± 5.21%, P = 0.039). Our study suggests intravitreal steroids (triamcinolone, dexamethasone implants) significantly reduce HEs in DME patients on short-term follow-up, whereas intravitreal bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.


Outcomes with Preoperative Biliary Stenting After Pancreaticoduodenectomy In the Modern Era.
Previous studies have documented increased complications following pancreaticoduodenectomy in patients who undergo preoperative biliary stenting (PBS). However, in the modern era, the vast majority of patients with jaundice are stented. We hypothesized that there is no difference in short-term postoperative outcomes between PBS and no PBS in patient with obstructive jaundice undergoing pancreaticoduodenectomy. We performed an analysis using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) participant use file (2014-2017). Patients who received neoadjuvant chemotherapy and required stenting were excluded from the analysis. A propensity-matched analysis was performed to select obstructive jaundice patients who underwent PBS and those who did not with similar characteristics prior to pancreaticoduodenectomy. Short-term postoperative outcome measures included superficial surgical site infection (S-SSI), deep surgical site infection (D-SSI), hospital length of stay (LOS), postoperative pancreatic fistula (POF), hospital readmission, minor morbidity (Clavien-Dindo I-II), major morbidity (Clavien-Dindo III, IV, V), and 30-day mortality. A total of 5851 patients with obstructive jaundice underwent pancreaticoduodenectomy without neoadjuvant chemotherapy. 81.6% underwent PBS. Based on the propensity-matched analysis, 927 patients who received PBS and 927 patients who did not were selected for comparing the outcomes between the two groups. There was no significant difference in outcome measures between the two groups with respect to S-SSI (OR 1.30 , 95% CI = 0.94-1.80, p = 0.12), D-SSI (OR 1.07, 95% CI = 0.81-1.41, p = 0.62), POF (OR 1.11, 95% CI = 0.87-1.42, p = 0.40), hospital readmission (OR 0.99, 95% CI = 0.77-1.27, p = 0.94), minor morbidity (OR 0.91, 95% CI = 0.76-1.11, p = 0.36), major morbidity (OR 0.84, 95% CI = 0.67-1.06, p = 0.14), and 30-day mortality (OR 1.05, 95% CI = 0.57-1.95, p = 0.87). Patients who underwent PBS were more likely to have shorter LOS (RR 0.87, 95% CI = 0.81-0.93, p < 0.0001). Contrary to previously reported studies, there was no increased risk of short-term postoperative outcomes after pancreaticoduodenectomy between PBS and N-PBS in a propensity-matched analysis. Preoperative biliary stenting is safe and does not need to be avoided before surgical intervention in patients who present with obstructive jaundice.


Intracellular Pressure Dynamics in Blebbing Cells.
Blebs are pressure-driven protrusions that play an important role in cell migration, particularly in three-dimensional environments. A bleb is initiated when the cytoskeleton detaches from the cell membrane, resulting in the pressure-driven flow of cytosol toward the area of detachment and local expansion of the cell membrane. Recent experiments involving blebbing cells have led to conflicting hypotheses regarding the timescale of intracellular pressure propagation. The interpretation of one set of experiments supports a poroelastic model of the cytoplasm that leads to slow pressure equilibration when compared to the timescale of bleb expansion. A different study concludes that pressure equilibrates faster than the timescale of bleb expansion. To address this discrepancy, a dynamic computational model of the cell was developed that includes mechanics of and the interactions among the cytoplasm, the actin cortex, the cell membrane, and the cytoskeleton. The model results quantify the relationship among cytoplasmic rheology, pressure, and bleb expansion dynamics, and provide a more detailed picture of intracellular pressure dynamics. This study shows the elastic response of the cytoplasm relieves pressure and limits bleb size, and that both permeability and elasticity of the cytoplasm determine bleb expansion time. Our model with a poroelastic cytoplasm shows that pressure disturbances from bleb initiation propagate faster than the timescale of bleb expansion and that pressure equilibrates slower than the timescale of bleb expansion. The multiple timescales in intracellular pressure dynamics explain the apparent discrepancy in the interpretation of experimental results.


The clinical significance of EphA2 and Ephrin A-1 in epithelial ovarian carcinomas.
To examine the expressions of the protein and mRNA of EPHA2 and EphrinA-1 in epithelial ovarian carcinomas/ovarian cancer cell lines and explore their prognostic value. To validate the immunohistochemical method, two ovarian cancer cell lines (OVCAR3 and SKOV3) were examined with RT-PCR, Western blot, and immunohistochemistry for EphA2 and EphrinA-1 expressions. Tumors from 118 patients with advanced epithelial ovarian cancer were then evaluated for EPHA2 and Ephrin A-1 protein expression, and frozen tissues from 30 cases were used for laser capture microdissection (LCM) assistant RT-PCR RNA analysis. 11 (9.3%), 67 (56.8%), 26 (22.0%), and 14 (11.9%) tumors demonstrated negative, weak, moderate, and strong EphA2 protein expressions, respectively, while 3 (2.5%), 67 (56.8%), 32 (27.1%), and 16 (13.8%) tumors were negative, weak, moderate, and strong for Ephrin A-1 protein expression, respectively. Variable amount of mRNA expression was observed in the 30 tumors analyzed by the method of LCM assistant RT-PCR. There was a trend for association between higher levels of either EphA2 or Ephrin A-1 expression and higher histological grade (P = 0.05 for both factors). No significant correlation between the expressions of EphA2 or Ephrin A-1 and age, histological type, and FIGO stage was observed. Patients with higher levels of EphA2 protein expressions had significantly shorter survival. Cox multivariate analyses revealed that residual tumor after surgery, histological type, and EphA2 protein expression were of independent prognostic significance. High level of EphA2 protein expression is significantly associated with a shorter patient survival and EphA2 receptor is a valuable prognostic marker for ovarian carcinoma.


Functional characterization of the p53 binding site in the human PYNOD promoter.
Many members of the NOD-like receptor (NLR) family play important roles in pathogen recognition and inflammation. However, human PYNOD, an NLR-like protein consisting of a pyrin domain and a nucleotidebinding and oligomerization domain (NOD), has been reported to inhibit inflammatory signals. Using bioinformatics, we found a completely preserved canonical p53 binding site in the PYNOD core promoter (-228 to -237 bp) both in humans and in chimpanzees. In this study, we investigated the characterization and biologic function of this binding site in vitro. The results show that either deletion of the p53 binding elements within the PYNOD promoter or treatment with p53 inhibitor (PFT-α) could significantly reduce PYNOD promoter activity and PYNOD expression as detected by the enhanced green fluorescent protein (EGFP) reporter system, reverse transcription-polymerase chain reaction, and Western blot respectively. Furthermore, the chromatin immunoprecipitation (ChIP) method confirmed that p53 could bind to the PYNOD promoter. Our findings suggest that the p53 binding site plays a positive role in regulating PYNOD gene expression, which may maintain an efficient balance between defense and self-inflicted injury in respond to pathogen invasion.


The E1beta and E2 subunits of the Bacillus subtilis pyruvate dehydrogenase complex are involved in regulation of sporulation.
The pdhABCD operon of Bacillus subtilis encodes the pyruvate decarboxylase (E1alpha and E1beta), dihydrolipoamide acetyltransferase (E2), and dihydrolipoamide dehydrogenase (E3) subunits of the pyruvate dehydrogenase multienzyme complex (PDH). There are two promoters: one for the entire operon and an internal one in front of the pdhC gene. The latter may serve to ensure adequate quantities of the E2 and E3 subunits, which are needed in greater amounts than E1alpha and E1beta. Disruptions of the pdhB, pdhC, and pdhD genes were isolated, but attempts to construct a pdhA mutant were unsuccessful, suggesting that E1alpha is essential. The three mutants lacked PDH activity, were unable to grow on glucose and grew poorly in an enriched medium. The pdhB and pdhC mutants sporulated to only 5% of the wild-type level, whereas the pdhD mutant strain sporulated to 55% of the wild-type level. This difference indicated that the sporulation defect of the pdhB and pdhC mutant strains was due to a function(s) of these subunits independent of enzymatic activity. Growth, but not low sporulation, was enhanced by the addition of acetate, glutamate, succinate, and divalent cations. Results from the expression of various spo-lacZ fusions revealed that the pdhB mutant was defective in the late stages of engulfment or membrane fusion (stage II), whereas the pdhC mutant was blocked after the completion of engulfment (stage III). This analysis was confirmed by fluorescent membrane staining. The E1beta and E2 subunits which are present in the soluble fraction of sporulating cells appear to function independently of enzymatic activity as checkpoints for stage II-III of sporulation.


The Streptomyces coelicolor ssgB gene is required for early stages of sporulation.
ssgB was identified as a novel early sporulation gene in Streptomyces coelicolor. An ssgB deletion mutant failed to sporulate, over-produced actinorhodin, and its colonies were significantly larger than those of the parental strain, suggesting an important role for the ssgB gene product in the process of growth cessation prior to sporulation-specific cell division. This places ssgB temporally before the paralogous sporulation gene ssgA. Analysis of ssgB mutant hyphae by electron microscopy and by confocal fluorescence microscopy showed that it was defective in the initiation of sporulation, as no sporulation septa could be identified, and DNA segregation had not yet been initiated in the mutant.


Biochar-induced changes in soil microbial affect species of antimony in contaminated soils.
Antimony (Sb) is a highly toxic heavy metal, and the amount of Sb in the soil is increasing due to anthropogenic activities. Recently, biochar (BC) has been used for remediation of Sb-contaminated soil, therefore, understanding the effect of BC-induced changes in soil microbial on the change of Sb speciation will help to elucidate the mechanism of BC in immobilization/mobilization of Sb in contaminated soils. Sb-contaminated soil with 10 wt % of Wheat straw-derived BC (SBC) and fruit (apple) tree-derived BC (FBC) and control was incubated for 130 days. Changes of soil bacterial community composition and Sb oxidation gene induced by BC were explored during the incubation. Dynamic change of Sb speciation was assessed by the citric acid extraction. The redundancy analysis (RDA) and spearman analysis (PCA) was used to analyze the relationship between Sb immobilization/mobilization and change of soil bacterial community induced by BC. The soil properties change induced by BC affected soil bacterial community composition, and Sb mobilization was strongly related to the change of soil bacterial community composition. The relative abundance of Sb oxidation gene increased in the soil amended by BC, which proved that oxidation of Sb(III) after 20 d incubation with SBC and 50 d incubation with FBC incubation. It is noteworthy that the application of BC has a potential mobilizing risk for Sb and both the change of soil bacteria and soil chemical properties play an important role in Sb mobilization. The possible risks induced by BC should be considered before applying the BC to Sb contaminated soil.


Adjuvant chemoimmunotherapy following regional therapy for isolated recurrences of breast cancer (stage IV NED).
A combination of 5-fluorouracil, Adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in breast cancer patients following surgical excision and/or radiation of first site of recurrent disease. In a group of 68 patients treated with FAC-BCG, the estimated proportion remaining free of disease at 2 years from first recurrence was 69%, compared to 24% in 60 historical control patients (P less than 0.01). Estimated 2-year survival rate from first recurrence was 85% for the FAC-BCG patients and 78% for the controls (P = 0.07). This regimen has significantly prolonged the disease-free interval from the first recurrence, but additional follow-up is needed to determine its effect on long-term survival.