Uniparental disomy of chromosome 21: A statistical approach and application in paternity tests.
Considering the overall frequency of paternity investigation cases including mutational events, there is a real possibility that at least a fraction of all inconsistencies reported in paternity cases are caused not by polymerase slippage mutations, but to chromosomic abnormalities, as Uniparental Disomy (UPD). We report here the investigation of a trio paternity case (mother, child and alleged father), with observed inconsistencies that can alternatively be explained by occurrence of maternal uniparental isodisomy of chromosome 21 (miUPD21). A total of 350 short tandem repeat (STR) and single nucleotide polymorphism (SNP) markers were tested, statistically suggesting true biological linkage within the trio. Additionally, we propose miUPD21 explains, with significantly greater probability, the occurrence of detected inconsistencies, when compared to alternative hypothesis of multiple and simultaneous slippage mutations. Similar cases could have their statistical conclusions improved or even altered by including unusual chromosomal segregation patterns in the hypothesis formulation, as well as in mathematical calculations. Such reports of allelic inconsistencies being explained by chromosomal alterations are common in clinical genetics, and such situations might have impact on forensic investigation.


Modern PID/FOPID controllers for frequency regulation of interconnected power system by considering different cost functions.
This article presents frequency regulation of an interconnected three-area power system (Thermal + Wind + Hydro). Fractional Order PID (FOPID) and Proportional-Integral-Derivative (PID) controllers are applied as subsidiary regulators to control the electrical power interconnected system at the time of sudden load variation. To accomplish this study, Genetic Algorithm (GA), Grey Wolf Optimizer (GWO), Sine Cosine Inspired Algorithm (SCIA) and Atom Search Inspired Algorithm (ASIA) are implemented to optimize the secondary regulators' gains (PID and FOPID) by considering various cost functions such as Integral Absolute Error (IAE), Integral Time Absolute Error (ITAE), Integral Square Error (ISE), and Integral Time Square Error (ITSE). Performance analysis in this work is conducted using various cost functions based on GA, GWO, SCIA and ASIA. The comparative analysis of the attained results reveals that GWO-PID and ASIA-PID settle at (83.83 s) and (30.31 s), respectively and ASIA-FOPID at (25.12 s). The controllers based on ITSE as a cost function outperform the comptrollers with other cost functions (ISE, IAE and ITAE). In addition, the ISE-based GA-PID and SCIA-PID settle at (113.92 s) and (35.1 s), respectively and SCIA-FOPID at (24.78 s). The ISE-based regulators yield improved response equated to other cost functions (ITSE, IAE and ITAE) optimized controllers. The robustness test also is carried out to validate the effectiveness of the proposed optimization techniques by changing the system parameters within ± 25% and ± 50% from their nominal values as well as changing the load pattern.


Associations of short-term exposure to air pollution and increased ambient temperature with psychiatric hospital admissions in older adults in the USA: a case-crossover study.
Little is known about the associations between ambient environmental exposures and the risk of acute episodes of psychiatric disorders. We aimed to estimate the link between short-term exposure to atmospheric pollutants, temperature, and acute psychiatric hospital admissions in adults aged 65 years and older in the USA. For this study, we included all people (aged ≥65 years) enrolled in the Medicare programme in the USA who had an emergency or urgent hospital admission for a psychiatric disorder recorded between Jan 31, 2000, and Dec 31, 2016. We applied a case-crossover design to study the associations between short-term exposure to air pollution (fine particulate matter [PM2·5], ozone, and nitrogen dioxide [NO2]), ambient temperature, and the risk of acute hospital admissions for depression, schizophrenia, and bipolar disorder in this population. The percentage change in the risk of hospital admission and annual absolute risk differences were estimated. For each 5°C increase in short-term exposure to cold season temperature, the relative risk of acute hospital admission increased by 3·66% (95% CI 3·06-4·26) for depression, by 3·03% (2·04-4·02) for schizophrenia, and by 3·52% (2·38-4·68) for bipolar disorder in the US Medicare population. Increased short-term exposure to PM2·5 and NO2 was also associated with a significant increase in the risk of acute hospital admissions for psychiatric disorders. Each 5 μg/m3 increase in PM2·5 was associated with an increase in hospital admission rates of 0·62% (95% CI 0·23-1·02) for depression, 0·77% (0·11-1·44) for schizophrenia, and 1·19% (0·49-1·90) for bipolar disorder; each 5 parts per billion (ppb) increase in NO2, meanwhile, was linked to an increase in hospital admission rates of 0·35% (95% CI 0·03-0·66) for depression and 0·64% (0·20-1·08) for schizophrenia. No such associations were found with warm season temperature. In the US Medicare population, short-term exposure to elevated concentrations of PM2·5 and NO2 and cold season ambient temperature were significantly associated with an increased risk of hospital admissions for psychiatric disorders. Considering the increasing burden of psychiatric disorders in the US population, these findings suggest that intervening on air pollution and ambient temperature levels through stricter environmental regulations or climate mitigation could help ease the psychiatric health-care burden. US National Institute of Environmental Health Sciences, US Environmental Protection Agency, and US National Institute on Aging.


The Alzheimer's Prevention Registry: A Large Internet-Based Participant Recruitment Registry to Accelerate Referrals to Alzheimer's-Focused Studies.
Recruitment for Alzheimer's disease (AD)-focused studies, particularly prevention studies, is challenging due to the public's lack of awareness about study opportunities coupled with studies' inclusion and exclusion criteria, resulting in a high screen fail rate. To develop an internet-based participant recruitment registry for efficiently and effectively raising awareness about AD-focused study opportunities and connecting potentially eligible volunteers to studies in their communities. Individuals age 18 and older are eligible to join the Alzheimer's Prevention Registry (APR). Individuals provide first and last name, year of birth, country, and zip/postal code to join the APR; for questions regarding race, ethnicity, sex, family history of AD or other dementia, and diagnosis of cognitive impairment, individuals have the option to select "prefer not to answer." The APR website maintains a list of recruiting studies and contacts members who have opted in by email when new studies are available for enrollment. As of December 1, 2019, 346,661 individuals had joined the APR. Members had a mean age of 63.3 (SD 11.7) years and were predominately women (75%). 94% were cognitively unimpaired, 50% reported a family history of AD or other dementia, and of those who provided race, 76% were white. 39% joined the APR as a result of a paid social media advertisement. To date, the APR helped recruit for 82 studies. The APR is a large, internet-based participant recruitment registry designed to raise awareness about AD prevention research and connect members with enrolling studies in their communities. It has demonstrated the ability to recruit and engage a large number of highly motivated members and assist researchers in meeting their recruitment goals. Future publications will report on the effectiveness of APR for accelerating recruitment and enrollment into AD-focused studies.


Opioidergic manipulations affect intake of 3% NaCl in sodium-deficient rats.
On six weekly occasions, a 3% NaCl solution was presented along with water to rats for 2 h 1 day after being treated with furosemide, a diuretic/natriuretic drug that causes a strong hunger for 3% NaCl. On some of the days, the sodium-hungry rats were injected with morphine in doses ranging from 0.3 to 10.0 mg/kg. Morphine produced biphasic effects on intake of 3% NaCl, with doses of 0.3-3.0 mg/kg increasing intakes dose dependently and 10.0 mg/kg decreasing intakes. The 3.0-mg/kg dose nearly doubled rats' mean intake of 3% NaCl. In contrast, naltrexone, an opioid receptor antagonist, reduced intake of 3% NaCl about 25-40% across doses ranging from 0.1 to 10.0 mg/kg. At some doses of morphine and naltrexone, NaCl ingestion was affected without significant influence of water intake. Therefore, it can be inferred that endogenous opioidergic systems participate in the control of NaCl drinking by sodium-deficient rats. The range of demonstrations of opioid involvement in the control of ingestion can now be extended to the hunger for hypertonic NaCl induced by sodium depletion.


Congenital anomalies associated with rhabdomyosarcoma: an autopsy study of 115 cases. A report from the Intergroup Rhabdomyosarcoma Study Committee (representing the Children's Cancer Study Group, the Pediatric Oncology Group, the United Kingdom Children's Cancer Study Group, and the Pediatric Intergroup Statistical Center).
Congenital anomalies were identified in 37 of 115 (32%) children and adolescents autopsied with rhabdomyosarcoma. An analysis of sex, age, site, and histology of cases with or without congenital anomalies showed no significant differences. Of the 45 identified anomalies, 14 were considered major and 31 minor. The distribution of the anomalies by system included central nervous (9), genitourinary (10), gastrointestinal (13), and cardiovascular systems (4). Ten patients had complex or miscellaneous anomalies. There was one child with each of the following: Rubinstein-Taybi syndrome, neurofibromatosis, single horseshoe kidney, hemihypertrophy, and Arnold-Chiari malformation. Aniridia was not noted in any case of rhabdomyosarcoma. Individuals with rhabdomyosarcoma have an increased incidence of genitourinary anomalies similar to that in Wilms' tumor. Recent molecular genetic investigations have suggested that rhabdomyosarcoma, Wilms' tumor, and hepatoblastoma share a common pathogenetic mechanism involving chromosome 11. The uniquely increased association of central nervous system anomalies with rhabdomyosarcoma and absence of aniridia would support a different gene locus operative on chromosome 11 for individuals with rhabdomyosarcoma compared to Wilms' tumor. Extensive epidemiologic studies now in progress in patients with rhabdomyosarcoma should provide the incidence of congenital anomalies and potential linkage with prenatal events.


MPO activity and generation of active O2 species in leukocytes from poorly controlled diabetic patients.
This study was undertaken to determine which part of ROI generation is reduced in the neutrophils from patients with NIDDM. Superoxide anion (O2-) production, LDCL activity in response to opsonized zymosan, and MPO activity were measured in leukocytes of poorly controlled NIDDM patients (FBG greater than 8.89 mM, HbA1 greater than 10%). In diabetic subjects, both O2- production and LDCL activity assessed with initial slope gradient and peak value were significantly reduced. MPO activity was also decreased in diabetic subjects, and there was a significant correlation between HbA1 levels and MPO activity of diabetic subjects. This study demonstrated that every step in leukocyte ROI generation should be reduced in the leukocytes from poorly controlled diabetic patients.


Molecular lipophilicity potential by CLIP, a reliable tool for the description of the 3D distribution of lipophilicity: application to 3-phenyloxazolidin-2-one, a prototype series of reversible MAOA inhibitors.
The capacity factor of eleven derivatives belonging to a prototype series of 3-phenyloxazolidin-2-one, reversible MAO inhibitors, was measured and compared to the calculated log Pcalc using the CLIP package. We demonstrate that this Molecular Lipophilicity Potential (MLP) approach is a valuable tool to estimate log Pcalc of such compounds.


Peptide thioester substrates for serine peptidases and metalloendopeptidases.
Peptide thioesters are sensitive substrates of various serine peptidases and metalloendopeptidases. Thioester substrates generally have high enzymatic hydrolysis rates and low background hydrolysis rates, and the hydrolysis rates can be easily monitored in the presence of thiol reagents such as 4,4'-dithiodipyridine or 5,5'-dithiobis (2-nitrobenzoic acid). Peptide thioester substrates have been invaluable for the study of enzyme specificity and enzyme inhibitors, especially in cases where no other practical synthetic substrates are available. Tripeptide substrates of the type Boc-Ala-Ala-AA-SBzl, where AA is nearly all of the 20 common amino acids, have now been synthesized and should be useful for the subsite mapping of new serine peptidases and the study of crude cell preparations containing serine peptidases.


Relationship between diastasis of the rectus abdominis muscle (DRAM) and musculoskeletal dysfunctions, pain and quality of life: a systematic review.
Diastasis of the rectus abdominis muscle (DRAM) is common during and after pregnancy. To determine the association between: the presence of DRAM and low back pain, lumbo-pelvic pain, incontinence, pelvic organ prolapse, abdominal muscle performance or health-related quality of life; and between DRAM width and severity of these outcomes. Six electronic databases (EMBASE, Medline, CINAHL, PUBMED, AMED and PEDro). Included studies of all designs with adults with DRAM that assessed low back pain, lumbo-pelvic pain incontinence, pelvic organ prolapse, abdominal performance or health-related quality of life. Methodological quality was assessed using the Effective Public Health Practice Project tool. A narrative summary was completed for DRAM presence and presence of the various musculoskeletal dysfunctions, and DRAM width and the severity of these dysfunctions. Twelve studies involving 2242 participants were included. There was no significant association between the presence of DRAM and lumbo-pelvic pain or incontinence. There was a small association between the presence of DRAM and pelvic organ prolapse. DRAM width may be associated with health-related quality of life, abdominal muscle strength and severity of low back pain. Quality of studies was weak. There was variability in the methods used to assess DRAM. There is weak evidence that DRAM presence may be associated with pelvic organ prolapse, and DRAM severity with impaired health-related quality of life, impaired abdominal muscle strength and low back pain severity. Systematic Review Registration Number: PROSPERO CRD42017058089.


Effects of simvastatin, bezafibrate and gemfibrozil on the quantity and composition of plasma lipoproteins.
Simvastatin, 10-40 mg/d (n = 11), bezafibrate, 600 mg/d (n = 6), and gemfibrozil, 1200 mg/d (n = 5) were administered for 12 weeks after a 4-week placebo period to subjects with initial plasma levels (mg/100 ml. mean +/- SD) of cholesterol (346 +/- 77), and of triglycerides (180 +/- 54). Total LDL-C plasma concentration was lowered 32% by simvastatin and 35% by bezafibrate, but only bezafibrate diminished the triglyceride (41%) and increased HDL-C plasma levels (35%). Plasma lipoprotein fractions obtained by discontinuous gradient ultracentrifugation, namely, VLDL, lighter LDL (LDL-1), heavier LDL (LDL-2) and bulk HDL were chemically analyzed. Simvastatin and bezafibrate significantly diminished the quantity of VLDL and LDL-1 particles, although barely modifying their composition. Neither drug influenced the LDL-2 plasma concentration. Bezafibrate increased the total plasma HDL level little interfering with its chemical composition. Gemfibrozil was the least effective of all drugs but decreased the lipid and protein contents and their ratios in VLDL and LDL-2.


Investigating Mitochondrial Transcriptomes and RNA Processing Using Circular RNA Sequencing.
Transcriptomic technologies have revolutionized the study of gene expression and RNA biology. Different RNA sequencing methods enable the analyses of diverse species of transcripts, including their abundance, processing, stability, and other specific features. Mitochondrial transcriptomics has benefited from these technologies that have revealed the surprising complexity of its RNAs. Here we describe a method based upon cyclization of mitochondrial RNAs and next generation sequencing to analyze the steady-state levels and sizes of mitochondrial RNAs, their degradation products, as well as their processing intermediates by capturing both 5' and 3' ends of transcripts.


The Cyclohexa-2,5-dienyl Group as a Placeholder for Hydrogen: Organocatalytic Michael Addition of an Acetaldehyde Surrogate.
An aldehyde with a cyclohexa-2,5-dienyl group in the α-position is introduced as a storable surrogate of highly reactive acetaldehyde. The cyclohexa-2,5-dienyl unit is compatible with an enantioselective Michael addition to nitroalkenes promoted by a Hayashi-Jørgensen catalyst and can be removed by a boron Lewis acid mediated C-C bond cleavage. The robust two-step sequence does not require a large excess of the aldehyde component that is typically needed when directly using acetaldehyde.


Children's comprehension of grammatical structures in context.
Children from nursery school, kindergarten, and first grade were asked to select pictures which correctly represented the propositional content of six grammatical structures-active, passive, cleft-agent, cleft-patient, prepositional beneficiary, indirect object-presented under three context conditions-appropriate, inappropriate, isolation. In the appropriate-context condition the relationship between the target structure and its prior context sentence followed known discourse regularities about the allocation of given and new information, while in the inappropriate-context condition the relationship between the target structure and prior context violated these discourse regularities. Comprehension of two of the grammatical structures tested--the passive and the cleft-patient--was better under the appropriate-context treatment than under the inappropriate-context treatment, indicating that young children are in fact sensitive to discourse regularities about the allocation of given and new information.


Tenets of PTEN tumor suppression.
Since its discovery as the elusive tumor suppressor gene at the frequently mutated 10q23 locus, PTEN has been identified as lost or mutated in several sporadic and heritable tumor types. A decade of work has established that PTEN is a nonredundant phosphatase that is essential for regulating the highly oncogenic prosurvival PI3K/AKT signaling pathway. This review discusses emerging modes of PTEN function and regulation, and speculates about how manipulation of PTEN function could be used for cancer therapy.


Redo Tracheostomy: Our Experience, Problems Encountered and How to Overcome Them.
Tracheostomy is a life-saving procedure done electively or most commonly in emergency basis. In patients with diagnosed case of cancer in upper airway tract they usually require tracheostomy at some point of time during their whole treatment procedure. Patients receiving radiotherapy or chemotherapy or combination of these are at high risk of developing post treatment changes in neck anatomy. Redo tracheostomy due to any reasons in such types of patients is a surgical challenge. The purpose of this article is to share our surgical technique in redo tracheostomy. During a period of two years 39 patients with diagnosed cancer in head neck region underwent redo tracheostomy at the hand of the author. Twenty-six patients were had received chemoradiation for their primary cancer and 6 patients were planned for second surgery due to recurrence disease in oral cavity. Reasons for redo tracheostomy are: sixteen patients were post chemoradiation on follow up with accidental expulsion of tube, 17 patients were recurrence/residual disease and 6 patients were plan for second surgery due to recurrence disease. In 9 cases the surgery was started by other doctor and taken over by the author due to profuse bleeding (5 cases) and failure to localised the trachea (4 cases). Among the 39 patients successful redo tracheostomy was possible in all. Mild surgical emphysema was encountered in 3 patients which was not significant. There was no other complication related to tracheostomy till the patients were discharge from the hospital. When redo tracheostomy is required in a post chemoradiation patients maintaining the proper dissection plane and procedure is important to avoid unnecessary complication intraoperatively.


Effect of microsolvation on zwitterionic glycine: an ab initio and density functional theory study.
The effect of microsolvation on zwitterionic glycine, considering both (-NH3(+)) as proton donor and (-COO(-)) as proton acceptor at correlated ab initio (MP2) level and density functional methods (B3LYP, PW91, MPW1PW91 and PBE) using 6-311++G** basis set has been reported. DFT methods have been employed so as to compare the performance/quality of different gradient-corrected correlation functionals (PW91, PBE), hybrid functionals (B3LYP, MPW1PW91) and to predict the near quantitative structural and vibrational properties, at reduced computational cost. B3LYP method outperforms among the different DFT methods for the computed hydrogen bond distances and found closer to the value obtained by correlated MP2 level, whereas MPW1PW91 and PBE methods shows very similar values but approximately 0.03 A less, compared to B3LYP method. MP2 calculation and single point CCSD(T)//MP2 calculation have been considered to decompose the interaction energy, including corrections for basis set superposition error (BSSE). Moreover, charge distribution analysis has also been carried out to understand the long raised questions, how and why the two body energies have significant contribution to the total binding energy.


Exogenous spermidine alleviates the adverse effects of aluminum toxicity on photosystem II through improved antioxidant system and endogenous polyamine contents.
Aluminum (Al) toxicity is a major yield-limiting factor for crops in acidic soils. In this work, we have investigated the potential role of spermidine (Spd) on Al toxicity in rice chloroplasts. Exogenous Spd markedly reduced Al concentration and elevated other nutrient elements such as Mn, Mg, Fe, K, Ca, and Mo in chloroplasts of Al-treated plants. Meanwhile, Spd further activated arginine decarboxylase (ADC) activity of key enzyme in polyamine (PA) synthesis, and enhanced PA contents in chloroplasts. Spd application dramatically addressed Al-induced chlorophyll (Chl) losses, inhibited thylakoid membrane protein complexes degradation, especially photosystem II (PSII), and significantly depressed the accumulations of superoxide radical (O2·-), hydrogen peroxide (H2O2), and malondialdehyde (MDA) in chloroplasts. Spd addition activated antioxidant enzyme activities and decreased soluble sugar content in chloroplasts compared with Al treatment alone. Spd not only reversed the inhibition of photosynthesis-related gene transcript levels induced by Al toxicity, but diminished the increased expression of Chl catabolism-related genes. Furthermore, Chl fluorescence analysis showed that Spd protected PSII reaction centers and photosynthetic electron transport chain under Al stress, thus improving photosynthetic performance. These results suggest that PAs are involved in Al tolerance in rice chloroplasts and can effectively protect the integrity and function of photosynthetic apparatus, especially PSII, by mitigating oxidative damage induced by Al toxicity.


Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis.
The aim was to evaluate whether patients with benign ovarian cysts, functional ovarian cysts, or endometriosis have an increased risk of developing gynecologic cancer. The Swedish Hospital Discharge Register was used to identify a cohort of women discharged from hospital with the diagnoses of ovarian cyst (n = 42217), functional ovarian cyst (n = 17998), or endometriosis (n = 28163). To each case, three controls were matched. The National Swedish Cancer Register matched all incident cancers diagnosed among cases and controls. From the Fertility Register, the date of birth of children born to the cases and controls were obtained. Women with endometriosis had an increased risk for ovarian cancer (OR 1.34; 95% CI 1.03-1.75), but no association was found between ovarian cysts or functional cysts and ovarian malignancy, including all ages. Young women (15-29 years old) discharged from hospital for ovarian cysts and functional cysts showed an increased risk of developing ovarian cancer later in life (OR 2.2; 95% CI 1.3-3.9 and OR 1.8; 95% CI 1.5-2.0), as well as women with ovarian cysts who had undergone ovarian cyst resection or unilateral oophorectomy (OR 8.8; 95% CI 5.2-15). The risk of developing ovarian cancer was inversely related to parity. Mean age at diagnosis was significantly lower in all three study groups. In this study women with endometriosis and young women who had undergone surgery with removal of an ovarian cyst had an increased risk of developing ovarian cancer.


Role of nocturnal arterial hypotension in optic nerve head ischemic disorders.
To investigate the role of nocturnal arterial hypotension, intraocular pressure (IOP) and heart rate in optic nerve head (ONH) ischemic disorders, and the effects of systemic factors and topical beta-blocker eye-drops on nocturnal arterial hypotension and heart rate. We investigated prospectively, by 24-hour ambulatory blood pressure (BP) monitoring and diurnal curve of the IOP, 275 white patients with anterior ischemic optic neuropathy (AION - 114), normal tension glaucoma (NTG - 131) and primary open angle glaucoma (POAG - 30). Hourly average BP data analyses showed a significantly greater drop in mean diastolic BP (p < 0.009) at night in NTG than AION. Cases with visual field deterioration had significantly (p = 0.05) lower minimum nighttime diastolic BP. Arterial hypertensives on oral hypotensive therapy showed a significantly lower mean nighttime systolic BP (p = 0.006) and larger mean percentage drop in systolic (p < 0.0001), diastolic (p = 0.0009) and mean (p < 0.0001) BPs. Normotensives and hypertensives without therapy had no such difference. IOP showed no significant correlation with visual field deterioration in any of these conditions. Patients using beta-blocker eyedrops, compared with those not using them, had greater percentage drop in diastolic BP (p = 0.028), lower minimum nighttime diastolic BP (p = 0.072) and lower minimum nighttime heart rate (p = 0.002). Findings of our study suggest that nocturnal hypotension, by reducing the ONH blood flow below a crucial level during sleep in a vulnerable ONH, may play a role in the pathogenesis of AION and glaucomatous optic neuropathy (GON) and progression of visual loss in them. Thus, nocturnal hypotension may be the final insult in a multifactorial situation.


Effects of high frequency oscillatory ventilation compared to conventional ventilation upon pulmonary vascular prostanoid production in neonatal piglets.
In order to investigate the possibility that high-frequency oscillatory ventilation (HFO) might preferentially stimulate intrapulmonary prostacyclin (PGI2) synthesis thereby decreasing pulmonary vascular smooth muscle tone, we determined pulmonary prostacyclin and thromboxane production in neonatal piglets ventilated by conventional means and by HFO (8 Hz). There was no detectable release of prostacyclin or thromboxane into blood passing through the lungs (i.e., pulmonary arterial concentrations were greater than aortic concentrations) during ventilation by conventional means or during HFO. Furthermore, there were no differences between the two modes of ventilation in cardiac output, systemic or pulmonary vascular resistance, or pulmonary vascular response to hypoxia/hypercapnia. We conclude that HFO does not stimulate pulmonary prostacyclin production and does not affect pulmonary vascular resistance or the pulmonary vasoconstriction associated with alveolar hypoxia/hypercapnia when compared to conventional ventilation in anesthetized newborn piglets.


Molecular epidemiology and antifungal susceptibility of Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis in Taiwan.
Candida parapsilosis was recently reclassified into 3 closely related species, C. parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis. Variation in susceptibility characteristics and prevalence of the 3 genomic species could have therapeutic and epidemiologic implications. The aim of this study is to characterize the genetic and antifungal susceptibility profiles of 97 C. parapsilosis isolates from 71 patients. Among the 71 nonduplicate isolates, 85.9% (61/71) were identified as C. parapsilosis sensu stricto, 5.6% (4/71) as C. metapsilosis, and 8.5% (6/71) as C. orthopsilosis species based on sequences of the internal transcribed spacer (ITS) region. The delineation of these 3 species is concordant with that achieved by pulsed-field gel electrophoresis of BssHII restriction fragments at 75% similarity. Antifungal susceptibility tests showed that most isolates were susceptible to flucytosine, azoles, amphotericin B, and echinocandins, whereas 3 C. metapsilosis isolates from 1 patient showed resistance and susceptible-dose dependence to fluconazole. The C. metapsilosis isolates exhibited significantly higher MIC values to both fluconazole and voriconazole than those of C. parapsilosis sensu stricto and C. orthopsilosis. On the other hand, the C. metapsilosis isolates showed significantly lower MIC values on 24 h to caspofungin than those of C. parapsilosis sensu stricto and C. orthopsilosis. For micafungin, the isolates of C. parapsilosis sensu stricto had significantly higher MIC values on 24 h than those of C. orthopsilosis and C. metapsilosis. Compared to Candida albicans, mutations from proline to alanine were identified on the hot spot 1 of Fks1 in all these C. parapsilosis sensu lato isolates regardless of their MIC levels. Some of the C. orthopsilosis and C. metapsilosis isolates expressed the isoleucine to valine substitution on the hot spot 2 region. However, the amino acid variations in these isolates did not correlate to their MIC values of echinocandin.


A Noninvasive Aid for Office-Based Gynecologists for the Diagnosis of Common External Genital Disorders.
Gynecology and dermatology share the diagnosis and the management of some disorders of the female external genital area. In the last decade, clinical diagnosis in dermatology has dramatically improved, thanks to the introduction of dermatoscopy. Dermatoscopy is a noninvasive, rapid, and simple technique performed with an affordable handheld instrument called dermatoscope, endowed with a light source and a high-quality lens achieving 10 times magnification. The use of dermatoscopy for the diagnosis of some common external genital disorders, i.e., genital warts (GW), vestibular papillomatosis (VP), molluscum contagiosum (MC), angiokeratoma (AK), and pediculosis pubis (PP), is presented and discussed. The use of dermatoscopy in a gynecologic office may considerably help the specialist to enhance in selected cases the clinical diagnosis and to avoid unnecessary and cumbersome investigations which may be time and money consuming.


Continuous versus intermittent sulphonylurea therapy in non-insulin-dependent diabetes mellitus.
Although it is 50 years since the discovery of the hypoglycaemic effects of sulphonylureas, the molecular basis of their effects are still not fully understood. It has been suggested that long term sulphonylurea therapy may desensitise the pancreatic beta-cells to further drug effects, and that intermittent sulphonylurea therapy may be the best approach to maintain their effectiveness. A randomised, double-blind study has been carried out to attempt to answer the question of whether intermittent sulphonylurea therapy is more effective then continuous administration. Responders to oral glibenclamide (glyburide) went on to receive continuous or intermittent treatment (glibenclamide for 2 weeks then placebo for 2 weeks) for 16 weeks. Glycaemic control was maintained in the continuous treatment group. However, glucose levels deteriorated in the intermittent treatment group, suggesting that there is no merit to intermittent sulphonylurea treatment. Other strategies to investigate include administration on an alternate-day basis or a shorter period off the drug (e.g. 1 week). The underlying question of optimal glycaemic control with sulphonylureas warrants a definitive answer.


Expression of expanded GGC repeats within NOTCH2NLC causes cardiac dysfunction in mouse models.
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by widespread intranuclear inclusions in the nervous system as well as multiple visceral organs. In 2019, expanded GGC repeats within the 5' untranslated region of the NOTCH2NLC gene was identified as the causative factor. NIID is a heterogeneous disorder with variable clinical manifestations including cognitive impairment, cerebellar ataxia, parkinsonism, paroxysmal symptoms, autonomic dysfunction, and muscle weakness. Although NIID primarily affects the central and peripheral nervous systems, growing evidence suggests potential cardiac abnormalities in NIID. However, the link between expanded GGC repeats within NOTCH2NLC and cardiac dysfunction remains uncertain. In this study, we utilized two transgenic mouse models, expressing NOTCH2NLC-(GGC)98 ubiquitously or specifically in cardiomyocytes, and identified p62 (also known as sequestosome 1, SQSTM1)-positive intranuclear NOTCH2NLC-polyG inclusions in cardiomyocytes in two mouse models. We observed that both models exhibited cardiac-related pathological and echocardiographic changes, albeit exhibiting varying degrees of severity. Transcriptomic analysis revealed shared downregulation of genes related to ion channels and mitochondria in both models, with the cardiomyocyte-specific mice showing a more pronounced downregulation of mitochondria and energy metabolism-related pathways. Further investigations revealed decreased expression of mitochondria-related genes and electron transport chain activity. At last, we conducted a retrospective review of cardiac-related examination results from NIID patients at our hospital and also identified some cardiac abnormalities in NIID patients. Our study provided the first in vivo evidence linking GGC repeat expansions within NOTCH2NLC to cardiac abnormalities and highlighted the contribution of mitochondrial dysfunction in the development of cardiac abnormalities.


The relationships of childhood socio-demographic factors and early parental loss to major depression in adult life.
Sixty middle-aged urban women with a major depressive episode (DSM-III) diagnosed in a community survey were compared with those 400 participants of the study who had no history of major depression. There were no significant differences between groups regarding most childhood demographic variables such as grade of urbanization, social class, school education, size of sibship and ordinal position. The subjects with major depression and especially those with melancholia had experienced parental loss before age 17 significantly more often than had the controls. This difference dealt only with parental divorce and other separations but not with parental death. There were no significant differences regarding parental death between melancholics, non-melancholic major depressives and controls.


Technoeconomic and life cycle analysis of soluble dietary fiber concentrate production from waste orange peels.
This research aims to optimize the environmentally sustainable and economically feasible process for soluble dietary fiber concentrate (SDFC) production from waste citrus peel by different physical methods, including micronization, autoclave, autoclave followed by micronization, extrusion, and ultrasonication. The study is mainly divided into two sections. The first section deals with a detailed life cycle assessment (LCA) of the size 40 kg SDFC/batch process and investigates the influence of various renewable energy sources, including biomass, solar, and wind electricity, on the environmental impact and compares it with mixed grid electricity. It was observed that the use of solar and wind electricity reduces CO2 emissions by 95.93 % and 99.07 %, respectively. In the second section, technoeconomic analysis (TEA) was performed of all processes for the same capability as LCA, with sensitivity analysis to investigate the influence of batch size by varying batch size from 10 kg to 250 kg to investigate the impact of scale-up from pilot to industrial scale. Moreover, study the impact of energy sources from mixed-grid to renewable energy on total plant economics. TEA shows that extrusion performs the best among all, with an internal rate of return of 43.77 %. Whereas by using solar-based electricity, the overall utility cost is reduced by 58 % compared to the mix grid electricity.


TMEM70 forms oligomeric scaffolds within mitochondrial cristae promoting in situ assembly of mammalian ATP synthase proton channel.
Mitochondrial ATP-synthesis is catalyzed by a F1Fo-ATP synthase, an enzyme of dual genetic origin enriched at the edge of cristae where it plays a key role in their structure/stability. The enzyme's biogenesis remains poorly understood, both from a mechanistic and a compartmentalization point of view. The present study provides novel molecular insights into this process through investigations on a human protein called TMEM70 with an unclear role in the assembly of ATP synthase. A recent study has revealed the existence of physical interactions between TMEM70 and the subunit c (Su.c), a protein present in 8 identical copies forming a transmembrane oligomeric ring (c-ring) within the ATP synthase proton translocating domain (Fo). Herein we analyzed the ATP-synthase assembly in cells lacking TMEM70, mitochondrial DNA or F1 subunits and observe a direct correlation between TMEM70 and Su.c levels, regardless of the status of other ATP synthase subunits or of mitochondrial bioenergetics. Immunoprecipitation, two-dimensional blue-native/SDS-PAGE, and pulse-chase experiments reveal that TMEM70 forms large oligomers that interact with Su.c not yet incorporated into ATP synthase complexes. Moreover, discrete TMEM70-Su.c complexes with increasing Su.c contents can be detected, suggesting a role for TMEM70 oligomers in the gradual assembly of the c-ring. Furthermore, we demonstrate using expansion super-resolution microscopy the specific localization of TMEM70 at the inner cristae membrane, distinct from the MICOS component MIC60. Taken together, our results show that TMEM70 oligomers provide a scaffold for c-ring assembly and that mammalian ATP synthase is assembled within inner cristae membranes.


Weight gain during pregnancy: A narrative review on the recent evidences.
Gestational weight gain is necessary for the normal fetus development, in fact a series of studies have evidenced that both low and excessive gestational weight gain is associated with negative fetal-neonatal outcomes. So, evidences on the optimal gestational weight gain across the ranges of the pre-pregnancy maternal body mass index are necessary. In this context, while for normal weight and underweight the recommendations of IOM are clearly stated and supported by well designed and conducted clinical studies, those for the obese pregnant women are even today debated. Pre-pregnancy obesity is associated with high risk to develop hypertension, gestational diabetes, cesarean section and high birth weight. The Institute of Medicine guidelines, in 2009, recommended that women with obesity gain 11-20 lb at a rate of 0.5 lb/week during the second and third trimesters of pregnancy. Successively, taking into account a series of meta-analysis, the American College of Obstetricians and Gynecologists emphasized that the IOM weight gain targets for obese pregnant women are too high. However the high risk to have babies small for gestational age, related to a low weight gain or a losing of weight during pregnancy, has also been demonstrated. More recent studies have taken into consideration the maternal and fetal outcomes of obese pregnant women with different obesity class (I,II,III) and different weight gain during pregnancy. The analysis of these studies, discussed in this narrative review, show that the appropriate gestational weight gain should be personalized considering the three obesity class; furthermore both an upper and lower limit of gestational weight gain should be reconsidered in order to prevent the negative maternal and fetal outcomes in these women.


Influence of diagnostic classification on outcomes and charges in geriatric assessment and rehabilitation.
To determine if diagnostic classification is associated with different outcomes from treatment on a geriatric assessment unit (GAU) compared with usual care for elderly patients with acute illnesses. Reanalysis after post-hoc diagnostic classification of a randomized clinical trial with one year follow up. Community hospital with rehabilitation facility. A total of 155 subjects, mean age 78 years and 78% female, of whom 58 subjects had a rehabilitation classification of their diagnoses and 97 had a medical or surgical classification. Mortality, nursing home use, activities of daily living, and charges for subsequent medical services. Mortality was decreased in persons with a rehabilitation classification who had received the GAU intervention. The GAU increased point-prevalence residence in the community for persons with a rehabilitation classification. For persons with a medical-surgical classification, the GAU intervention was associated with decreased cumulative use of nursing homes. However, GAU intervention was also associated with trends for increased charges in both diagnostic classification groups, even when adjusted for differential survival. Greater benefit from the GAU intervention on mortality and maintenance of residence in the community was observed in a group with a rehabilitation classification when compared with a group with a medical-surgical classification. These improved outcomes in the rehabilitation group were not accompanied by decreased charges for later medical services that could compensate for initial rehabilitation charges.


Emotional reactions of patient, family, and staff in acute-care period of spinal cord injury: part 2.
Part 1 of this paper, published in the last issue, dealt with the sequence of emotional reactions of patients in the Spinal Cord Injury Center at New York University Hospital. Part 2, presented here, considers the reactions of family members and staff through these same stages of shock, denial, anger, and depression, and further discusses implications for treatment.


MAGE-I proteins and cancer-pathways: A bidirectional relationship.
Data emerged from the last 20 years of basic research on tumor antigens positioned the type I MAGE (Melanoma Antigen GEnes - I or MAGE-I) family as cancer driver factors. MAGE-I gene expression is mainly restricted to normal reproductive tissues. However, abnormal re-expression in cancer unbalances the cell status towards enhanced oncogenic activity or reduced tumor suppression. Anomalous MAGE-I gene re-expression in cancer is attributed to altered epigenetic-mediated chromatin silencing. Still, emerging data indicate that MAGE-I can be regulated at protein level. Results from different laboratories suggest that after its anomalous re-expression, specific MAGE-I proteins can be regulated by well-known signaling pathways or key cellular processes that finally potentiate the cancer cell phenotype. Thus, MAGE-I proteins both regulate and are regulated by cancer-related pathways. Here, we present an updated review highlighting the recent findings on the regulation of MAGE-I by oncogenic pathways and the potential consequences in the tumor cell behavior.


Does rest breed rust? An examination of DNP-Rest decisions and performance in the National Basketball Association regular and post-season.
Within the National Basketball Association (NBA), players and teams maintain that having healthy players sit out some games during the regular season may help them be more productive during the post-season. This decision to not play in order to rest the player, aptly noted as a DNP-Rest decision on injury reports, is in line with team and player goals, and fits with a growing body of evidence in support of the power of rest for health and performance. However, these practices conflict with some goals of the league, which has a vested interest in having the top talent play to attract broadcasters, advertisers, live spectators, and thus, enhance viewership. The current study is among the first to test the theory that strategically resting healthy players during the regular season results in better performance, as indicated by Player Efficiency Rating (PER) and Win Shares, during the post-season. Utilizing data from the 2016-17 through the 2020-21 NBA seasons, there was not sufficient evidence to suggest that resting more games during the regular season results in better performance in the post-season. Findings from a nested case-control study of 184 players (92 cases; 92 controls) also showed no differences in the change in performance from regular to post-season between cases of players who received rest during the regular season and matched controls. Although the restorative effects of rest might be considerable in the short term, the current study provides additional evidence to suggest that the impact may not carry over into the post-season.


One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema.
To compare different doses and dosing regimens of Vascular Endothelial Growth Factor (VEGF) Trap-Eye with laser photocoagulation in eyes with diabetic macular edema (DME). Randomized, double-masked, multicenter, phase 2 clinical trial. Diabetic patients (n = 221) with center-involved DME. Participants were assigned randomly to 1 of 5 treatment regimens: VEGF Trap-Eye 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); or 2 mg dosing as needed after 3 initial monthly doses (2PRN), or macular laser photocoagulation. The change in best-corrected visual acuity (BCVA) at 24 weeks (the primary end point) and at 52 weeks, proportion of eyes that gained 15 letters or more in Early Treatment of Diabetic Retinopathy Study (ETDRS) BCVA, and mean changes in central retinal thickness (CRT) from baseline. As previously reported, mean improvements in BCVA in the VEGF Trap-Eye groups at week 24 were 8.6, 11.4, 8.5, and 10.3 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus 2.5 letters for the laser group (P ≤ 0.0085 versus laser). Mean improvements in BCVA in the VEGF Trap-Eye groups at week 52 were 11.0, 13.1, 9.7, and 12.0 letters for 0.5q4, 2q4, 2q8, and 2PRN regimens, respectively, versus -1.3 letters for the laser group (P ≤ 0.0001 versus laser). Proportions of eyes with gains in BCVA of 15 or more ETDRS letters at week 52 in the VEGF Trap-Eye groups were 40.9%, 45.5%, 23.8%, and 42.2% versus 11.4% for laser (P = 0.0031, P = 0.0007, P = 0.1608, and P = 0.0016, respectively, versus laser). Mean reductions in CRT in the VEGF Trap-Eye groups at week 52 were -165.4 μm, -227.4 μm, -187.8 μm, and -180.3 μm versus -58.4 μm for laser (P < 0.0001 versus laser). Vascular Endothelial Growth Factor Trap-Eye generally was well tolerated. The most frequent ocular adverse events with VEGF Trap-Eye were conjunctival hemorrhage, eye pain, ocular hyperemia, and increased intraocular pressure, whereas common systemic adverse events included hypertension, nausea, and congestive heart failure. Significant gains in BCVA from baseline achieved at week 24 were maintained or improved at week 52 in all VEGF Trap-Eye groups. Vascular Endothelial Growth Factor Trap-Eye warrants further investigation for the treatment of DME.


Impact of gender on treatment and outcome of ICU patients.
Gender modifies immunologic responses caused by severe trauma or critical illness. The aim of this study was to investigate the impact of gender on hospital mortality, length of intensive care unit (ICU) stay, and intensity of care of patients treated in ICUs. Data on 24,341 ICU patients were collected from a national database. We measured severity of illness with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and intensity of care with Therapeutic Intervention Scoring System (TISS) scores. We used logistic regression analysis to test the independent effect of gender on hospital mortality. We compared the lengths of ICU stay and the intensity of care of men and women. Male gender was associated with increased hospital mortality among postoperative ICU patients [adjusted odds ratio 1.33 (95% confidence interval 1.12-1.58, P = 0.001)] but not among medical patients [adjusted odds ratio 1.02 (95% confidence interval 0.92-1.13, P = 0.74)]. Male gender was associated with an increased risk of death particularly in the oldest age group (75 years or older) and among the patients with relatively low APACHE II scores (<16). Mean length of ICU stay was 3.2 days for men and 2.6 days for women (P < 0.001). Male patients comprised 61.7% of the study population but consumed 66.0% of days in intensive care. Male gender contributes to poor outcome in postoperative ICU patients. Approximately two-thirds of ICU resources are consumed by male patients.


Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective.
Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.


The role of arthroscopy in the assessment and treatment of tibial plateau fractures.
This retrospective study compared arthroscopic treatment of certain tibial plateau fractures to traditional open techniques. From January 1989 through August 1992, 40 patients with tibial plateau fractures were evaluated. After reviewing the records and radiologic studies, 23 patients were included in the study based on fracture patterns. Using Hohl's revised classification system, patients with either local compression or split compression fractures were included. Twelve of these patients were treated with arthroscopic reduction and percutaneous fixation (ARPF; group A). The remaining 11 underwent open reduction and internal fixation (ORIF; group B). The results of the ARPF group were superior to those of the ORIF group. In the ARPF group, all reductions were anatomic and remained fixed at least 3 months postoperatively, whereas only six (55%) of the ORIF patients had anatomic reductions initially. Furthermore, one of these patients had further loss of reduction on follow-up radiographs. Iliac crest bone graft was used in two patients in group A and 10 in group B. The use of bone graft in the arthroscopically treated group had no effect on the final outcome. The average length of postoperative hospitalization for the ARPF patients with isolated tibial plateau fractures was 5.36 days compared with 10.27 days for patients who were treated with ORIF. Average time to full weight bearing was 8.95 weeks in the ARPF group and 12.30 weeks in the ORIF group. No patients in either group had medial collateral ligament repairs. No ARPF-treated patients experienced valgus laxity after treatment. One patient in the ORIF group had residual instability and another walked with a cane.(ABSTRACT TRUNCATED AT 250 WORDS)


Contact order dependent protein folding rates: kinetic consequences of a cooperative interplay between favorable nonlocal interactions and local conformational preferences.
Physical mechanisms underlying the empirical correlation between relative contact order (CO) and folding rate among naturally occurring small single-domain proteins are investigated by evaluating postulated interaction schemes for a set of three-dimensional 27mer lattice protein models with 97 different CO values. Many-body interactions are constructed such that contact energies become more favorable when short chain segments sequentially adjacent to the contacting residues adopt native-like conformations. At a given interaction strength, this scheme leads to folding rates that are logarithmically well correlated with CO (correlation coefficient r = 0.914) and span more than 2.5 orders of magnitude, whereas folding rates of the corresponding Gō models with additive contact energies have much less logarithmic correlation with CO and span only approximately one order of magnitude. The present protein chain models also exhibit calorimetric cooperativity and linear chevron plots similar to that observed experimentally for proteins with apparent simple two-state folding/unfolding kinetics. Thus, our findings suggest that CO-dependent folding rates of real proteins may arise partly from a significant positive coupling between nonlocal contact favorabilities and local conformational preferences.


Determination of Chloramphenicol and Nitrofuran Metabolites in Cobia, Croaker, and Shrimp Using Microwave-Assisted Derivatization, Automated SPE, and LC-MS/MS-Results from a U.S. Food and Drug Administration Level Three Inter-Laboratory Study.
An interlaboratory study was conducted to test a published, peer-reviewed manuscript in the Journal of AOAC INTERNATIONAL Vol 98, No. 3, 2015, "Quantitation of Chloramphenicol and Nitrofuran Metabolites in Aquaculture Products Using Microwave-Assisted Derivatization, Automated Solid-Phase Extraction, and LC-MS/MS." The purpose of this study was to demonstrate the performance of the method in shrimp, cobia, and croaker matrices. Three U.S. Food and Drug Administration laboratories participated in the collaborative study. The laboratories tested matrix blanks and laboratory-fortified matrix blanks at various levels in three separate matrices. The method evaluation included determination of the LOQ, accuracy, and precision. The reproducibility and repeatability of the RSD, % levels for matrix spikes fortified below the action level were < 10% for all residues in shrimp, < 13% for all residues in cobia except for 3-amino-2-oxazolidinone which was ≤ 22%, and < 16% for croaker. The RSD, % levels for all other spikes in the study were < 14%. Average percent recoveries for all matrices ranged from 81.6% - 102%. The study demonstrated that the method is acceptable for use for the combined determination of chloramphenicol and nitrofuran metabolites in the study matrices. The study showed acceptable quantitation for the high-throughput chloramphenicol and nitrofuran metabolites method.


Size-dependent effects of layered double hydroxide nanoparticles on cellular functions of mouse embryonic stem cells.
Layered double hydroxide nanoparticles (LDH NPs) are promising for stem cell research and applications. In this study, we investigated the size-dependent interactions of LDH NPs with mouse embryonic stem cells (mESCs). LDH NPs with diameters of 100 and 50 nm were synthesized and characterized. mESCs were cultured to undergo spontaneous differentiation. After incubation with LDH NPs, cytotoxicity, cellular uptake, pluripotency, differentiation and epithelial-mesenchymal transition process of mESCs were assessed. LDH NPs with the size of 50 nm induced higher cellular uptake and more outstandingly inhibited spontaneous differentiation and epithelial-mesenchymal transition process. Our research demonstrated the size-dependent effects of LDH NPs on controlling fate and cellular functions of mESCs.


Enhanced production of polyhydroxyalkanoates in Pseudomonas putida KT2440 by a combination of genome streamlining and promoter engineering.
Polyhydroxyalkanoates (PHAs), a class of bioplastics produced by a variety of microorganisms, have become the ideal alternatives for oil-derived plastics due to their superior physicochemical and material characteristics. Pseudomonas putida KT2440 can produce medium-chain-length PHA (mcl-PHA) from various substrates. In this study, a novel strategy of the large-scale deletion of genomic islands (GIs) coupling with promoter engineering was developed in P. putida KT2440 for constructing the minimal genome cell factories (MGF) capable of efficiently producing mcl-PHA. Firstly, P. putida KTU-U13, a 13 GIs- and upp-deleted mutant derived from the parental strain P. putida KT2440, was used as a starting strain for further deletion of GIs to generate a series of genome-reduced strains. Subsequently, the two minimal genome strains KTU-U24 and KTU-U27, which had a 7.19% and 8.35% reduction relative to the genome size of KT2440 and were advantageous over the strain KTU (KT2440∆upp) and KTU-U13 in several physiological traits such as the maximum specific growth rate, plasmid transformation efficiency, heterologous protein expression capacity and PHA production capacity, were selected as the chassis cells for PHA metabolic engineering. To prevent the formation of the by-product gluconic acid, the glucose dehydrogenase gene was deleted in KTU-U24 and KTU-U27, resulting in KTU-U24∆gcd and KTU-U27∆gcd. To enhance the transcriptional level of PHA synthase genes (phaC) and the supply of the precursor acetyl-CoA, a strong endogenous promoter P46 was inserted into upstream of the phaC operon and pyruvate dehydrogenase gene in the genome of KTU-U24∆gcd and KTU-U27∆gcd, to generate KTU-U24∆gcd-P46CA and KTU-U27∆gcd-P46CA, with the PHA yield of 50.5 wt% and 53.8 wt% (weight percent of PHA in cell dry weight). Finally, KTU-U27∆gcd-P46CA, the most minimal KT2440 chassis currently available, was able to accumulate the PHA to 55.82 wt% in a 5-l fermentor, which is the highest PHA yield obtained with P. putida KT2440 so far. This study suggests that genome streamlining in combination with promoter engineering may be a feasible strategy for the development of the MGF for the efficient production of high value products. Moreover, further streamlining of the P. putida KT2440 genome has great potential to create the optimal chassis for synthetic biology applications.


Psychological and neurobiological mechanisms underlying the decline of maternal behavior.
The maternal behavior decline is important for the normal development of the young and the wellbeing of the mother. This paper reviews limited research on the factors and mechanisms involved in the rat maternal behavior decline and proposes a multi-level model. Framed in the parent-offspring conflict theory (an ultimate cause) and the approach-withdrawal model (a proximate cause), the maternal behavior decline is viewed as an active and effortful process, reflecting the dynamic interplay between the mother and her offspring. It is instigated by the waning of maternal motivation, coupled with the increased maternal aversion by the mother in responding to the changing sensory and motoric patterns of pup stimuli. In the decline phase, the neural circuit that mediates the inhibitory ("withdrawal") responses starts to increase activity and gain control of behavioral outputs, while the excitatory ("approach") maternal neural circuit is being inhibited or reorganized. Various hormones and certain monoamines may play a critical role in tipping the balance between the excitatory and inhibitory neural circuits to synchronize the mother-infant interaction.


High volume on line hemodiafiltration in dialysis pregnant patients: predilutional or postdilutional?
Although the frequency of pregnancy in women on chronic dialysis is extremely low, it is associated with severe maternal and perinatal morbidity and mortality. This situation represents a challenge for the therapeutic team, which requires multidisciplinary management, as well as measures to adequate dialysis treatment. Such efforts include increasing the time and frequency of dialysis session, maintaining low uremia levels and ensuring hemodynamic stability by avoiding intra-treatment arterial hypotension and hydro electrolytic fluctuations. Regarding the dialysis modality, literature makes references to hemodialysis or peritoneal dialysis in pregnancy women, but little is known about the of high volume online hemodiafiltration (HVHDF) as well as the appropriate type of replacement fluid (pre-dilution or post-dilution). We present two cases of patients who were pregnant while being treated with HVHDF modality and had a favorable evolution, where the decision to continue with this dialysis modality was motivated by a best hemodynamic stability and the highest clearance of all types of uremic toxins offered by HVHDF.


Transitional cell carcinoma of the bladder: low incidence of human papillomavirus DNA detected by the polymerase chain reaction and in situ hybridization.
Viral studies on mammalian urothelium have shown an association between the bovine papillomavirus and cancer of the bladder in cattle. However, the evidence for human papillomavirus (HPV) involvement in urinary bladder in man is less clear. The aim of this study was to investigate the association between HPV DNA and transitional cell carcinoma of the bladder, using the highly sensitive polymerase chain reaction (PCR) and non-isotopic DNA in situ hybridization of formalin-fixed paraffin-embedded tissues from 76 patients. An HPV type specific set of primers was localized on the E6-gene for HPV 16/18 DNA. The second and third set of primers were specific for HPV 6/11 DNA. A biotinylated DNA probe which recognizes HPV 6/11, 16/18, and 31/33/35 was used for in situ hybridization. Of the 76 cases investigated, PCR analysis showed positive signals in seven (9.2%) of cases--six for HPV 16 DNA, and one for HPV 16 DNA and HPV 6 DNA. Four (5.2%) were also reactive for HPV 16/18 DNA using in situ hybridization. Most transitional cell carcinomas (71.4%) associated with HPV DNA were of high pathological grade/stage. One case had koilocytosis. Our results suggest that HPV DNA in transitional cell carcinoma is probably a rare occurrence, although the finding on the high risk HPV 16 DNA may indicate a role for it in this tumour's aetiology.


Urinary steroid profile in early pregnancy after in vitro fertilization.
The aim of the study was to compare the levels of urinary steroid metabolites of patients with successful in vitro fertilization and patients who failed to achieve pregnancy. Comparison of urinary steroid profiles prior to oocyte pick-up and three weeks after embryo transfer. University hospital. Eleven women in the same age range with pregnancy after in vitro fertilization and eleven women who failed to achieve pregnancy. The standard "long" protocol was used for ovarian stimulation and intracytoplasmic sperm injection for assisted in vitro fertilization. The steroid metabolites in urine samples collected for 24 h were determined by gas chromatography-mass spectrometry. Steroid metabolite levels in urine samples determined in the early pregnancy period. The levels of androsterone, etiocholanolone, pregnanediol, tetrahydro-11-dehydrocorticosterone and tetrahydro-corticosterone were significantly higher (p < 0.05) in the urine of women with successful pregnancy three weeks after the embryo transfer, while the levels of tetrahydrocortisone, tetrahydrocortisol, allo-tetrahydrocortisol and α-cortolone became higher in the group of patients with unsuccessful pregnancy. The production of androgens, progesterone and corticoid steroid metabolites is altered in the early pregnancy period after in vitro fertilization.


Investigation of the Role of Impeller Structural Parameters on Liquid-Liquid Mixing Characteristics in Stirred Tanks.
Liquid-liquid mixings in stirred tanks are commonly found in many industries. In this study, we performed computational fluid dynamics (CFD) modeling and simulation to investigate the liquid-liquid mixing behavior. Furthermore, the population balance model (PBM) was used to characterize the droplet size distribution. The PBM model parameters were calibrated using the experimental data of droplet sizes at different agitation speeds. Additionally, we employed the steady-state Sauter mean droplet size to validate the developed CFD-PBM coupled model at different dispersion phase holdups. Then, the validated CFD-PBM coupled model was employed to evaluate the role of impeller structural parameters on the liquid-liquid mixing efficiency based on a user-defined mixing index. It was found that the position of impellers significantly affects the mixing efficiency, and an increase in stirring speed and the number of impellers improved the mixing efficiency.


Reported incidence of fever for under-5 children in Zambia: a longitudinal study.
Childhood fever is the most common clinical sign of Plasmodium falciparum infection. It is used as a measure of burden of the disease and the effectiveness of control programs for malaria. This study aimed to determine the incidence of fever in under-5 children of Magoye and Chivuna rural areas of Mazabuka district, Zambia. Incidence of fever was evaluated longitudinally over a period of 16 months (July 2006 and November 2007) among children aged 12-59 months in Magoye and Chivuna rural communities. The data was collected for a study on community directed treatment of soil-transmitted helminth infections in under-five children. Data from caretakers of 1221 children were collected using a structured interviewer-administered questionnaire. Cox proportion hazard regression was used to determine predictors of multiple episodes of fever and Kaplan-Meier survival curves was used to compare survival between two groups. A total of 1221 under-5 children [median age 32 months; IQR 12-58] participated in the study and 696 (57 %) were from Magoye and 525 (43 %) from Chivuna. The incidence rate of fever was 162.4 per month per 1000 children for the 16 months period. The proportion of fever was not statistically related to children' age [p = 0.779] and sex [p = 0.546]. Predictors of multiple episodes of fever were: age (37-48 vs. 12-24 months) [HR 0.81; 95 % CI 0.67, 0.98; p = 0.030]; location (Chivuna vs. Magoye) [HR 1.35; 95 % CI 1.17, 1.56; p < 0.001]; and season (dry vs. rainy) [HR 0.17; 95 % CI 0.12, 0.23; p < 0.001]. The study has shown that the incidence of fever was high in the study areas. Febrile illnesses like malaria still have a significant effect on the health of under-5 children in the study population. There still exists the need for interventions aimed at reducing the incidence of fever in under five children, more especially in rural areas.


Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk.
The understanding of the pathophysiology of atherosclerosis has advanced greatly in the past decade. Cardiovascular risk factors increase the likelihood of an adverse event by having a detrimental effect on the blood vessel wall. Abnormal interactions among cholesterol, inflammatory mediators, platelets and the vascular wall lead to atherogenesis and cardiac events. In an effort to better understand this process, develop surrogate end points for clinical trials and, ultimately, better risk stratify individuals, a variety of measures of arterial function have been studied. These include measures of endothelial health and arterial compliance. The current paper reviews the various techniques available for the study of vascular health. While not yet routinely used for clinical care, these measurements provide important insights into the pathophysiology and treatment of atherosclerosis.


Comparison of device-based therapy options for heart failure with preserved ejection fraction: a simulation study.
Successful therapy of heart failure with preserved ejection fraction (HFpEF) remains a major unmet clinical need. Device-based treatment approaches include the interatrial shunt device (IASD), conventional assist devices pumping blood from the left ventricle (LV-VAD) or the left atrium (LA-VAD) towards the aorta, and a valveless pulsatile assist device with a single cannula operating in co-pulsation with the native heart (CoPulse). Hemodynamics of two HFpEF subgroups during rest and exercise condition were translated into a lumped parameter model of the cardiovascular system. The numerical model was applied to assess the hemodynamic effect of each of the four device-based therapies. All four therapy options show a reduction in left atrial pressure during rest and exercise and in both subgroups (> 20%). IASDs concomitantly reduce cardiac output (CO) and shift the hemodynamic overload towards the pulmonary circulation. All three mechanical assist devices increase CO while reducing sympathetic activity. LV-VADs reduce end-systolic volume, indicating a high risk for suction events. The heterogeneity of the HFpEF population requires an individualized therapy approach based on the underlying hemodynamics. Whereas phenotypes with preserved CO may benefit most from an IASD device, HFpEF patients with reduced CO may be candidates for mechanical assist devices.


Orbital cystic neurinoma.
A 64-year-old woman presented with a 6-month history of exophthalmus of her right eye. She had no neurological deficit except for the exophthalmus and numbness in the right side of her forehead (frontal nerve territory). Neuro-imaging demonstrated a cystic mass in the right orbit. The tumour was totally removed by microsurgical transcranial surgery. The histological diagnosis was neurinoma. The origin of the tumour was considered to be the frontal nerve. Only two other cases of orbital cystic neurinoma have been reported. This rare clinical entity should be included in the differential diagnosis of a cystic mass in the orbit.


Mental effort required for walking: effects of retinitis pigmentosa.
To determine whether retinitis pigmentosa (RP) increases the mental effort required for walking. A dual-task methodology was used; walking speed and reaction time (RT) to randomly emitted tones were measured in 13 persons with RP and 29 persons with normal vision. Measures of RT were used to estimate the mental effort required for walking. In a second experiment, 15 persons with RP and 17 persons with normal vision navigated a "simple" and a "complex" route. The RP subjects had longer RT compared with the normal-vision subjects when walking the complex but not the simple route. Normalized to each person's baseline, RT while walking the complex route was significantly correlated with log contrast sensitivity (r = -0.63) and log retinal area (r = -0.64) in the RP group. The amount of mental effort required for walking was shown to also depend on familiarity with the route. Route complexity is critical in determining whether walking requires more mental effort for persons with RP than for persons with normal vision. The magnitude of mental effort required for mobility covaries with the visual impairment measures which correlate with mobility performance in RP.


The changing scene in health care management.
Health care systems aren't what they used to be...and are changing, as is current thinking on how a health care organization should be administered. Below, Gillian Biscoe looks at today's health care scenario and finds a place for nurses in it.


G protein coupling to the thrombin receptor in Chinese hamster lung fibroblasts.
The specific involvement of G proteins in thrombin receptor-mediated Ca2+ mobilization and DNA synthesis has been studied in single Chinese hamster lung fibroblasts (CCL39 cells) activated by the hexapeptide SFLLRN. Immunoblots performed with antibodies directed against the COOH terminus of G protein alpha subunits revealed that alpha q, alpha i, and alpha o were each present in CCL39 cells. The Ca2+ response to SFLLRN was measured after microinjection of anti-alpha q or anti-alpha o antibodies, which produced a total blockade in 71 and 46% of cells, respectively. A partial inhibition of the SFLLRN-induced Ca2+ response was observed in the remaining cells. The lag time between exposure of the cells to SFLLRN and the onset of Ca2+ mobilization was significantly longer (20-24 s) in cells microinjected with anti-alpha q- or anti-alpha o-antibodies than in control cells microinjected with preimmune serum (9 +/- 1 s). Moreover, the peak height of the Ca2+ response to SFLLRN was decreased by 36 and 73%, respectively in cells microinjected with anti-alpha q or anti-alpha o antibodies. SFLLRN-induced DNA synthesis in growth-arrested CCL39 cells was also inhibited (44-78%) by prior microinjection of anti-alpha q or anti-alpha o antibodies. Anti-alpha 1 antibodies had no effect on the SFLLRN-induced Ca2+ response or on DNA synthesis. These results provide direct evidence that the thrombin receptor in CCL39 cells is coupled to two different types of G proteins, Gq and Go, both causing Ca2+ mobilization and mitogenesis.


Identification and characterization of CBL and CIPK gene families in eggplant (Solanum melongena L.).
Eggplant (Solanum melongena L.) is an edible vegetable cultivated and consumed worldwide. But the production of eggplant is significantly limited by the soil salinization in greenhouse cultivation system. The main ions are Na(+), Ca(2+), Mg(2+), K(+), Cl(-), and SO4 (2-) in the salty soils. Calcineurin B-like proteins (CBLs) are calcium sensors and control the affinities and activities of numerous ion transporters with CBL-interacting protein kinases (CIPKs). In this study, a total of 5 CBL and 15 CIPK genes from eggplant were identified first. The yeast two-hybrid (Y2H) assay and bimolecular fluorescence complementation (BiFC) assay demonstrated the interaction network between SmCBLs and SmCIPKs. Strikingly, some new CBL-CIPK complexes were found which have never been discovered in any other plant species. The expression level of each SmCBL or SmCIPK under 200 mM NaCl, low potassium (LK; 100 μM), high Mg with 20 mM MgCl2 and MgSO4 stresses were examined by quantitative real-time PCR (qRT-PCR) assay and these CBL and CIPK genes were found to respond to the four ion stresses differently. Interestingly, the differential expression level of SmCIPK3, -24 or -25 to Mg(2+) is higher than Na(+), and Cl(-) is higher than SO4 (2-). In addition, different magnesium salt can induce different response mechanisms in eggplant. In summary, this study provides insight into the characterization of CBLs and CIPKs in eggplant. It may be used in a novel biotechnological breeding program strategy to create new eggplant cultivars, leading to enhance different ion tolerance.


RyR2/IRBIT regulates insulin gene transcript, insulin content, and secretion in the insulinoma cell line INS-1.
The role of ER Ca2+ release via ryanodine receptors (RyR) in pancreatic β-cell function is not well defined. Deletion of RyR2 from the rat insulinoma INS-1 (RyR2KO) enhanced IP3 receptor activity stimulated by 7.5 mM glucose, coincident with reduced levels of the protein IP3 Receptor Binding protein released with Inositol 1,4,5 Trisphosphate (IRBIT). Insulin content, basal (2.5 mM glucose) and 7.5 mM glucose-stimulated insulin secretion were reduced in RyR2KO and IRBITKO cells compared to controls. INS2 mRNA levels were reduced in both RyR2KO and IRBITKO cells, but INS1 mRNA levels were specifically decreased in RyR2KO cells. Nuclear localization of S-adenosylhomocysteinase (AHCY) was increased in RyR2KO and IRBITKO cells. DNA methylation of the INS1 and INS2 gene promotor regions was very low, and not different among RyR2KO, IRBITKO, and controls, but exon 2 of the INS1 and INS2 genes was more extensively methylated in RyR2KO and IRBITKO cells. Exploratory proteomic analysis revealed that deletion of RyR2 or IRBIT resulted in differential regulation of 314 and 137 proteins, respectively, with 41 in common. These results suggest that RyR2 regulates IRBIT levels and activity in INS-1 cells, and together maintain insulin content and secretion, and regulate the proteome, perhaps via DNA methylation.


Laser Doppler velocimetry (LDV) and 3D phase-contrast magnetic resonance angiography (PC-MRA) velocity measurements: validation in an anatomically accurate cerebral artery aneurysm model with steady flow.
To verify the accuracy of velocity mapping with three-dimensional (3D) phase-contrast magnetic resonance angiography (PC-MRA) for steady flow in a realistic model of a cerebral artery aneurysm at a 3T scanner. Steady flow through an original geometry model of a cerebral aneurysm was mapped at characteristic positions by state-of-the-art laser Doppler velocimetry (LDV) as well as 3D PC-MRA at 3T. The spatial distributions and local values of two velocity components obtained with these two measurement methods were compared. The 3D PC-MRA velocity field distribution and mean velocity values exhibited only minor differences to compare to the LDV measurements in straight artery regions for both main and secondary velocities. The differences increased in regions with disturbed flow and in cases where the measurement plane was not perpendicular to the main flow direction. 3D PC-MRA can provide reliable measurements of velocity components of steady flow in small arteries. The accuracy of such measurements depends on the artery size and the measurement plane positioning.


The presence of collagenase in collagen preparations.
The frequently observed instability of neutral salt solutions of native collagen extracted from various sources and partially purified by standard procedures has been studied by disc electrophoresis in polyacrylamide gel and by electron microscopic examination of segment long spacing crystallites. The phenomenon has revealed time and temperature dependency, pH optima near neutrality, and inhibition by sodium EDTA and serummin addition, collagen breakdown has been found to be quantitatively related to the state of aggregation of the substrate, being more marked in reconstituted collagen gels than in collagen in solutionma typical pattern of animal collagenase degradation of native collagen into two fragments designated as TC-A and TC-B has been observed under certain conditions. It is concluded that the degradation of native collagen in neutral salt solution is due to a specific collagenase, and that this enzyme probably remains bound to collagen throughout the process of extraction and partial purification. Experiments with gelatin suggest that, in addition to collagenase, a nonspecific proteolytic activity may also be present in collagen preparations.


Synthesis of potentially new schiff bases of N-substituted-2-quinolonylacetohydrazides as anti-COVID-19 agents.
We report herein a new series of synthesized N-substituted-2-quinolonylacetohydrazides aiming to evaluate their activity towards SARS-CoV-2. The structures of the obtained products were fully confirmed by NMR, mass, IR spectra and elemental analysis as well. Molecular docking calculations showed that most of the tested compounds possessed good binding affinity to the SARS-CoV-2 main protease (Mpro) comparable toRemdesivir.


Amplitude spectral analysis of maturational changes of delta waves in preterm infants.
The aim of this study is to clarify the usefulness of amplitude spectral analysis for an evaluation of maturational changes of delta activities in preterm infants. We chose each ten healthy infants without complications who were 29-30, 31-32, and 33-34 weeks of post-conceptional age (PCA) at electroencephalogram (EEG) recordings. Fast Fourier transform algorithm was applied for amplitude spectral analysis. The analyzed data were divided into four frequency bands; D1 0.53-1, D2 1-2, D3 2-3, and D4 3-4Hz. The average amplitude of six segments with high voltage slow waves was calculated in each frequency band. A significant reduction of the amplitude along with PCA was present in all leads in D1 band. On the other hand, a significant negative correlation with PCA was observed only in the occipital leads in D2, D3 or D4 bands. In conclusion, maturational EEG changes assessed by amplitude spectral analysis were prominent in the occipital areas, and in the frequency less than 1Hz.


The public health informatics infrastructure: anticipating its role in cancer.
Cancer information and surveillance, historically conducted with manual data collection and submission, are viewed increasingly as inherently dependent on the effective application of information science. One challenge is to use information technology (IT) in a manner that improves cancer-related decision-making and ultimately the quality of care that is offered to patients with cancer. In this article we begin by envisioning a future view of IT-supported surveillance and care that can be made available for application in cancer and its management. We then ask what barriers need to be overcome and what forces are at work that may help us in our efforts to effect the necessary changes. Our future vision for surveillance and information, although appealing and widely shared, requires major cultural change, financial investment, and logistical planning. Competition in the medical marketplace, coupled with fiscal pressures affecting providers and health systems, suggests that leadership for regional and national coordination will need to come from elsewhere-and likely from governments.


Palliative excisional surgery for primary colorectal cancer in patients with incurable metastatic disease. Is there a survival benefit? A systematic review.
Patients with stage IV colorectal cancer with unresectable metastases can either receive chemotherapy or palliative resection of the primary lesion. In the absence of any randomized data the choice of initial treatment in stage IV colorectal cancer is not based on firm evidence. A search of MEDLINE, Pubmed, Embase and the Cochrane Library database was performed from 1980 to 2010 for studies comparing palliative resection in stage IV colorectal cancer with other treatment modalities. Audits and observational studies were excluded. Median survival was the primary outcome measure. The morbidity and mortality of surgical and nonsurgical treatments were compared. Twenty-one studies (no randomized controlled trials) were identified. Most demonstrated a survival benefit for patients who underwent palliative resection. Multivariate analysis indicates that tumour burden and performance status are both major independent prognostic variables. Selection bias, incomplete follow up and nonstandardized reporting of complications make the data difficult to interpret. The studies indicate that there may be a survival benefit for primary resection of colorectal cancer in stage IV disease. The findings suggest that resection of the primary tumour should be based on tumour burden and performance status rather than on the presence or absence of symptoms alone.


Differing Conceptualizations of the Goals of Care Discussion: A Critical Discourse Analysis.
The goals of care discussion (GOCD) has been positioned as an improvement strategy to address discordance between care decisions made by seriously ill patients and care received. Interventions aimed at improving GOCDs however have had limited success. This may in part be due to the considerable variation in views on the essential components and expected outcomes of a GOCD. This variability, and consequently clinical approaches to GOCDs, may reflect fundamental differences in how the GOCD is conceptualized. To identify and characterize differing conceptualizations of the GOCD. Critical discourse analysis was used to qualitatively examine GOCDs documented for inpatients of 35 Canadian palliative medicine (PM), critical care medicine (CCM) and general internal medicine (GIM) physicians. Patterns in the ways the GOCD had been constructed were characterized by identifying different aspects of the approaches used by clinicians. GOCD notes varied in the predominant style and tone (from narrative to biomedical), predominant information source (patient/family to physician), and contribution of the patient's perspective. Notably binary differences were also found in the locus of goals and located either with the patient or with the broad concept of treatments. Although not exclusively, locus of goals tended to be with the patient among PM physicians and with treatments among CCM and GIM physicians. These findings offer clinical evidence for differing conceptualizations of the GOCD and orientations to goals as either person-centered or treatment-centered. This phenomenon may be in part discipline-based and has important implications for both clinical practice and training experiences.


Review of leaching characteristics of triazines and their degradation products.
Only few data have been published on the environmental impact of pesticide degradation products on soil and groundwater. It is known that some of the degradation products of triazines, particularly those formed from N-dealkylation reactions, can be phytotoxic and more mobile than their parent compounds. In some cases it has been shown that they are present at even higher concentrations than the latter. Yet, their impact on groundwater quality is unknown since information on both environmental levels and chemiodynamic parameters are generally lacking. The conclusions of this work are that many triazine degradation products may pose a significant hazard to the quality of groundwater and that there is a need to promote and extend the production of experimental data on this topic.


Primary thymic adenocarcinoma coexisting with type AB thymoma: a rare case with long-term survival.
Thymic carcinoma is a rare tumor. The most common histological subtype is squamous cell carcinoma, and only a few cases of thymic adenocarcinoma have been reported. A case of papillary adenocarcinoma of thymic origin that coexisted with type AB thymoma as a separate nodule is presented herein. The patient was found to have an abnormal mediastinal shadow on chest X-ray. A computed tomography scan revealed a round, 6.5-cm-diameter mass in the right anterior mediastinum. The preoperative diagnosis was thymoma, and thymothymectomy was performed. On pathological examination, two tumors, which were diagnosed as papillary adenocarcinoma and type AB thymoma, respectively, were present in the thymus without any connection with each other. The patient has been alive without any signs of recurrence for 11 years after surgery. We diagnosed the adenocarcinoma in this case was a primary thymic carcinoma.


Insuring Care: Paperwork, Insurance Rules, and Clinical Labor at a U.S. Transgender Clinic.
What is a clinician to do when people needing medical care do not have access to consistent or sufficient health insurance coverage and cannot pay for care privately? Analyzing ethnographically how clinicians at a university-based transgender clinic in the United States responded to this challenge, I examine the U.S. health insurance system, insurance paperwork, and administrative procedures that shape transgender care delivery. To buffer the impact of the system's failure to provide sufficient health insurance coverage for transgender care, clinicians blended administrative routines with psychological therapy, counseled people's minds and finances, and leveraged the prestige of their clinic in attempts to create space for gender nonconforming embodiments in gender conservative insurance policies. My analysis demonstrates that in a market-based health insurance system with multiple payers and gender binary insurance rules, health care may be unaffordable, or remain financially challenging, even for transgender people with health insurance. Moreover, insurance carriers' "reliance" on clinicians' insurance-related labor is problematic as it exacerbates existing insurance barriers to the accessibility and affordability of transgender care and obscures the workings of a financial payment model that prioritizes economic expediency over gender nonconforming health.


Synthesis, proton and 13C NMR and reaction mechanism studies of novel isoindolones derivatives, obtained through TAWERS procedure.
A series of novel isoindolone derivatives (13-18) were prepared in goods yields by applying the TAWERS methodology. A general approach for formation of isoindolones from the aza-Wittig reaction of iminophosphoranes with dialdehydes under neutral and mild conditions was realized. Using 1D NMR a [1,3]-hydride migration was detected. The assignment of the structures and conformation behavior of the derivatives was achieved using 1D and 2D NMR (NOESY, DEPT, HMQC, and HMBC).


Porin pores of mitochondrial outer membranes from high and low eukaryotic cells: biochemical and biophysical characterization.
The mitochondrial porins from mammalian tissues and from low eukaryotic cells were purified with a high yield, and their biochemical and functional properties were investigated. When analyzed by SDS gel electrophoresis, all mammalian porins show a very similar apparent molecular mass (35-35.5 kDa). In contrast yeast and Paramecium porins have a molecular mass of 30 and 37 kDa, respectively. The peptide maps of mammalian porins are very similar although small differences are apparent between porins of different tissues of the same organism and also between those of the same tissue of different organisms. The peptide patterns of porins from yeast and Paramecium are completely different from those of mammalian porins. Antibodies raised against the rat liver porin cross-react with all the other mammalian porins but not with that of yeast. The incorporation of porins into artificial lipid bilayer membranes showed that they are able to form pores with approximately the same specific activity. The single-channel conductance is for all porins, except for that of Paramecium, about 4 nS in 1 M KCl, corresponding to an effective pore diameter of 1.7 nm. They are voltage-dependent and switch to substates at transmembrane potentials higher than 10 mV. The number of gating charges varies, however, for pores from different tissues, indicating a different sensitivity to the potential as a result of a possible different function.


[Melorheostosis and anterior cruciate ligament tear in a 15-year-old female].
We report the case of a 15-year-old girl who suffered an indirect knee trauma. The standard X-rays revealed a tract of ivory-like bone partially obstructing the medullary canal of the femur and the tibia. Magnetic resonance imaging produced a hypointense signal on the T1 and T2 sequences. The radiographic diagnosis was melorheostosis which was confirmed on the biopsy specimen which ruled out other diagnoses. The MRI also revealed a tear of the anterior cruciate ligament, treated conservatively. Clinical and radiological surveillance were proposed for the melorheostosis.


In vitro and in vivo studies of ambruticin (W7783): new class of antifungal antibiotics.
Ambruticin is a cyclopropyl-pyran acid, representing a new class of antibiotics. It has a relatively broad antifungal spectrum in vitro and is highly active against dimorphic as well as filamentous organisms. Of 24 strains of dermatophytic fungi tested, the majority were susceptible to ambruticin at 0.049 mug/ml or less. The minimal inhibitory concentration for the systemic fungi Histoplasma capsulatum and Blastomyces dermatitidis was 0.049 to 0.39 mug/ml. Ambruticin is fungicidal for metabolizing cells of Microsporum fulvum and does not cause cell leakage of 260-nm absorbing material. The antibiotic is effective orally as well as topically in guinea pigs experimentally infected with Trichophyton mentagrophytes. In mice, a single oral dose of 75 mg/kg produced peak serum levels of 45 mug/ml in 1 h with a serum half-life of 3.1 h. Excretion of the antibiotic is principally by the biliary route.


Biofabrication of a Functional Tubular Construct from Tissue Spheroids Using Magnetoacoustic Levitational Directed Assembly.
In traditional tissue engineering, synthetic or natural scaffolds are usually used as removable temporal support, which involves some biotechnology limitations. The concept of "scaffield" approach utilizing the physical fields instead of biomaterial scaffold has been proposed recently. In particular, a combination of intense magnetic and acoustic fields can enable rapid levitational bioassembly of complex-shaped 3D tissue constructs from tissue spheroids at low concentration of paramagnetic agent (gadolinium salt) in the medium. In the current study, the tissue spheroids from human bladder smooth muscle cells (myospheres) are used as building blocks for assembling the tubular 3D constructs. Levitational assembly is accomplished at low concentrations of gadolinium salts in the high magnetic field at 9.5 T. The biofabricated smooth muscle constructs demonstrate contraction after the addition of vasoconstrictive agent endothelin-1. Thus, hybrid magnetoacoustic levitational bioassembly is considered as a new technology platform in the emerging field of formative biofabrication. This novel technology of scaffold-free, nozzle-free, and label-free bioassembly opens a unique opportunity for rapid biofabrication of 3D tissue and organ constructs with complex geometry.


A comprehensive review of the effects of resveratrol on glucose metabolism: unveiling the molecular pathways and therapeutic potential in diabetes management.
Resveratrol, a naturally occurring polyphenolic compound predominantly found in red wine and grapes, has garnered attention for its potential role in regulating carbohydrate digestion, glucose absorption, and metabolism. This review aims to deliver a comprehensive analysis of the molecular mechanisms and therapeutic potential of resveratrol in influencing vital processes in glucose homeostasis. These processes include carbohydrate digestion, glucose absorption, glycogen storage, insulin secretion, glucose metabolism in muscle cells, and triglyceride synthesis in adipocytes.The goal of this review is to offer an in-depth understanding of the multifaceted effects of resveratrol on glucose metabolism. By doing so, it presents valuable insights into its potential applications for preventing and treating metabolic disorders. This comprehensive examination of resveratrol's impact on glucose management will contribute to the growing body of knowledge on this promising natural compound, which may benefit researchers, healthcare professionals, and individuals interested in metabolic disorder prevention and treatment.


Synthesis and antituberculosis activity of the first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol.
The first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol moieties were synthesized and evaluated for inhibition activity against Mycobacterium tuberculosis H37Rv.


[Nifedipine as a coadjuvant drug in the treatment of uncontrolled epilepsy: a preliminary report].
The authors report the use of nifedipine as a coadjuvant drug in the treatment of three patients with uncontrolled epilepsy.


Vaccination uptake and awareness of a free hepatitis B vaccination program among female commercial sex workers.
We sought to explore the reach of a free hepatitis B vaccination program among female commercial sex workers (CSWs) within a legalized prostitution setting in the Netherlands. We also investigated the reasons for nonparticipation and noncompliance. In this cross-sectional study based on ethnographic mapping and targeted sampling, 259 CSWs were interviewed at their work in 3 regions in the Netherlands. The semistructured interviews contained questions on sociodemographics, sexual risk behavior, sex work, awareness of the opportunity to obtain free hepatitis B vaccination, vaccination uptake, and compliance with the full vaccination schedule. Of our sample, 79% reported awareness of the opportunity to obtain hepatitis B vaccination, and 63% reported to be vaccinated against hepatitis B (received > or =1 vaccination). A personal approach by health professionals or was associated with vaccination uptake, when specific sociodemographic variables, sexual behavior, and sex work related covariates were controlled for in the analysis. Window prostitution and the duration of working in the region were associated with awareness of the opportunity to obtain free hepatitis B vaccination. The results of this study suggest that outreach activities (i.e., a personal approach) within this program are beneficial. Transient CSWs are more difficult to reach within the current vaccination program. These results can be used to increase the success of future health programs among this risk group.