Racial differences in healthcare expenditures for prevalent multimorbidity combinations in the USA: a cross-sectional study.
We aimed to model total charges for the most prevalent multimorbidity combinations in the USA and assess model accuracy across Asian/Pacific Islander, African American, Biracial, Caucasian, Hispanic, and Native American populations. We used Cerner HealthFacts data from 2016 to 2017 to model the cost of previously identified prevalent multimorbidity combinations among 38 major diagnostic categories for cohorts stratified by age (45-64 and 65 +). Examples of prevalent multimorbidity combinations include lipedema with hypertension or hypertension with diabetes. We applied generalized linear models (GLM) with gamma distribution and log link function to total charges for all cohorts and assessed model accuracy using residual analysis. In addition to 38 major diagnostic categories, our adjusted model incorporated demographic, BMI, hospital, and census division information. The mean ages were 55 (45-64 cohort, N = 333,094) and 75 (65 + cohort, N = 327,260), respectively. We found actual total charges to be highest for African Americans (means $78,544 [45-64], $176,274 [65 +]) and lowest for Hispanics (means $29,597 [45-64], $66,911 [65 +]). African American race was strongly predictive of higher costs (p < 0.05 [45-64]; p < 0.05 [65 +]). Each total charge model had a good fit. With African American as the index race, only Asian/Pacific Islander and Biracial were non-significant in the 45-64 cohort and Biracial in the 65 + cohort. Mean residuals were lowest for Hispanics in both cohorts, highest in African Americans for the 45-64 cohort, and highest in Caucasians for the 65 + cohort. Model accuracy varied substantially by race when multimorbidity grouping was considered. For example, costs were markedly overestimated for 65 + Caucasians with multimorbidity combinations that included heart disease (e.g., hypertension + heart disease and lipidemia + hypertension + heart disease). Additionally, model residuals varied by age/obesity status. For instance, model estimates for Hispanic patients were highly underestimated for most multimorbidity combinations in the 65 + with obesity cohort compared with other age/obesity status groupings. Our finding demonstrates the need for more robust models to ensure the healthcare system can better serve all populations. Future cost modeling efforts will likely benefit from factoring in multimorbidity type stratified by race/ethnicity and age/obesity status.


Biosorption potential of the macrofungus Ganoderma carnosum for removal of lead(II) ions from aqueous solutions.
This paper reports the utilization of a macro-fungus Ganoderma carnosum as a biosorbent material for the removal of lead(II) ions from aqueous solutions. The biosorption potential of G. carnosum was investigated by batch experiments. The influences of physico-chemical parameters like pH, biosorbent dosage, contact time and initial metal ion concentration were evaluated. The biosorption equilibrium was attained in 10 minutes. Equilibrium biosorption data were analyzed by the Freundlich, Langmuir and Dubinin-Radushkevich (D-R) isotherm models. Maximum biosorption capacity of biosorbent was found to be 22.79 mg g(-1) (1.10 x 10(-4) mol g(-1)) at the pH value of 5.0. The biosorbent was regenerated using 10 mM HCl solution, with up to 96% recovery, and reused four times in biosorption-desorption cycles successively. Biosorption efficiency of G. carnosum was also examined in a real effluent. The mechanism of the biosorption was investigated with FTIR, SEM and EDAX analysis and the findings suggested that the biosorption process involved in ion exchange as dominant mechanism as well as complexation. The ion exchange mechanism was also confirmed by the mean free energy value obtained from D-R isotherm model.


Bacterial mechanisms to overcome inhibitory effects of dietary tannins.
High concentrations of tannins in fodder plants inhibit gastrointestinal bacteria and reduce ruminant performance. Increasing the proportion of tannin-resistant bacteria in the rumen protects ruminants from anti-nutritional effects. The reason for the protective effect is unclear, but could be elucidated if the mechanism(s) by which tannins inhibit bacteria and the mechanisms of tannin resistance were understood. A review of the literature indicates that the ability of tannins to complex with polymers and minerals is the basis of the inhibitory effect on gastrointestinal bacteria. Mechanisms by which bacteria can overcome inhibition include tannin modification/degradation, dissociation of tannin-substrate complexes, tannin inactivation by high-affinity binders, and membrane modification/repair and metal ion sequestration. Understanding the mechanism of action of tannins and the mechanism(s) bacteria use to overcome the inhibitory effects will allow better management of the rumen ecosystem to reduce the anti-nutritional effects of tannin-rich fodder plants and thereby improve ruminant production.


The cultivation bias: different communities of arbuscular mycorrhizal fungi detected in roots from the field, from bait plants transplanted to the field, and from a greenhouse trap experiment.
The community composition of arbuscular mycorrhizal fungi (AMF) was investigated in roots of four different plant species (Inula salicina, Medicago sativa, Origanum vulgare, and Bromus erectus) sampled in (1) a plant species-rich calcareous grassland, (2) a bait plant bioassay conducted directly in that grassland, and (3) a greenhouse trap experiment using soil and a transplanted whole plant from that grassland as inoculum. Roots were analyzed by AMF-specific nested polymerase chain reaction, restriction fragment length polymorphism screening, and sequence analyses of rDNA small subunit and internal transcribed spacer regions. The AMF sequences were analyzed phylogenetically and used to define monophyletic phylotypes. Overall, 16 phylotypes from several lineages of AMF were detected. The community composition was strongly influenced by the experimental approach, with additional influence of cultivation duration, substrate, and host plant species in some experiments. Some fungal phylotypes, e.g., GLOM-A3 (Glomus mosseae) and several members of Glomus group B, appeared predominantly in the greenhouse experiment or in bait plants. Thus, these phylotypes can be considered r strategists, rapidly colonizing uncolonized ruderal habitats in early successional stages of the fungal community. In the greenhouse experiment, for instance, G. mosseae was abundant after 3 months, but could not be detected anymore after 10 months. In contrast, other phylotypes as GLOM-A17 (G. badium) and GLOM-A16 were detected almost exclusively in roots sampled from plants naturally growing in the grassland or from bait plants exposed in the field, indicating that they preferentially occur in late successional stages of fungal communities and thus represent the K strategy. The only phylotype found with high frequency in all three experimental approaches was GLOM A-1 (G. intraradices), which is known to be a generalist. These results indicate that, in greenhouse trap experiments, it is difficult to establish a root-colonizing AMF community reflecting the diversity of these fungi in the field roots because fungal succession in such artificial systems may bias the results. However, the field bait plant approach might be a convenient way to study the influence of different environmental factors on AMF community composition directly under the field conditions. For a better understanding of the dynamics of AMF communities, it will be necessary to classify AMF phylotypes and species according to their life history strategies.


Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis.
To investigate the possible role of HIV infection in the natural history of chronic parenterally-acquired hepatitis C. A multicenter cross-sectional study was performed in 547 patients with chronic parenterally-acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV-negative). Approximate duration of HCV infection was estimated in all patients included, and histologic diagnoses made at different time intervals following HCV infection were analyzed in both groups. Factors related to serum HCV-RNA levels were also investigated. Histologic findings were similar in liver biopsies from both HIV-infected and noninfected patients. However, in the first 10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar results were found in the first 5 and 15 years, respectively, and most of the HIV-negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time interval longer than 15 years. Consequently, mean interval from estimated time of HCV infection to cirrhosis was significantly longer in HIV-negative than HIV-positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with and without cirrhosis) and long duration of HCV infection were significantly associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500 cells/ml (p < 0.05). HIV infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis C viremia levels and more severe liver damage.


Ral and Rheb GTPase activating proteins integrate mTOR and GTPase signaling in aging, autophagy, and tumor cell invasion.
Diverse environmental cues converge on and are integrated by the mTOR signaling network to control cellular growth and homeostasis. The mammalian Tsc1-Tsc2 GTPase activating protein (GAP) heterodimer is a critical negative regulator of Rheb and mTOR activation. The RalGAPα-RalGAPβ heterodimer shares sequence and structural similarity with Tsc1-Tsc2. Unexpectedly, we observed that C. elegans expresses orthologs for the Rheb and RalA/B GTPases and for RalGAPα/β, but not Tsc1/2. This prompted our investigation to determine whether RalGAPs additionally modulate mTOR signaling. We determined that C. elegans RalGAP loss decreased lifespan, consistent with a Tsc-like function. Additionally, RalGAP suppression in mammalian cells caused RalB-selective activation and Sec5- and exocyst-dependent engagement of mTORC1 and suppression of autophagy. Unexpectedly, we also found that Tsc1-Tsc2 loss activated RalA/B independently of Rheb-mTOR signaling. Finally, RalGAP suppression caused mTORC1-dependent pancreatic tumor cell invasion. Our findings identify an unexpected crosstalk and integration of the Ral and mTOR signaling networks.


Saccades under Mental Load in Infantile Nystagmus Syndrome and Controls.
This study compares saccades and visual task performance in patients with infantile nystagmus syndrome (INS) with that in normally sighted individuals under mental load. The results highlighted that to more completely evaluate INS therapies recognition time should also be measured with mental load, resembling real-world conditions. Patients with INS may complain of "being slow to see." Stress is reported to worsen nystagmus and to prolong visual recognition time. We hypothesized that the effects of mental load on timing indices of visual recognition, for example, saccade latency, target acquisition time, target viewing time, and subjects' reaction time, differ between the INS and control groups. Eye movements were recorded when participants (INS group, n = 15; controls, n = 25) reported the direction of tumbling-E targets presented randomly across ±25°. The task was repeated with both mental arithmetic and time restriction to impose high mental load, confirmed through subjective ratings and heart rate measurement. Mental load increased saccade latency (mean, 32.69 milliseconds; 95% confidence interval [CI], 21.17 to 44.20 milliseconds; P < .001) and target acquisition time (57.00 milliseconds; 95% CI, 34 to 81 milliseconds; P < .001). Patients with INS showed longer saccade latency (39.79 milliseconds; 95% CI, 23.98 to 55.62 milliseconds; P < .001) and target acquisition time (134.00 milliseconds; 95% CI, 96 to 172 milliseconds; P < .001) compared with controls. The interaction between task and group was significant for saccade gain (0.11; 95% CI, 0.02 to 0.19; P = .015), target acquisition time (37.93 milliseconds; 95% CI, 36.91 to 38.96 milliseconds; P = .011), and subjects' reaction time (95.37 milliseconds; 95% CI, 65.91 to 124.84 milliseconds; P = .043). There was an inverse correlation between the changes in subjects' response errors and target viewing time with mental load only for controls (r = -0.484, P = .014). Total foveation exposure time and target viewing time remained unchanged. Mental load worsens "being slow to see" in INS because of delayed target acquisition and possibly because efficiency of visual processing decreases more in patients with INS compared with controls. To investigate outcomes of INS therapies, visual recognition time should be also measured with mental load.


TNF-induced mitochondrial damage: a link between mitochondrial complex I activity and left ventricular dysfunction.
Mitochondrial damage is implicated in the progression of cardiac disease. Considerable evidence suggests that proinflammatory cytokines induce oxidative stress and contribute to cardiac dysfunction. This study was conducted to determine whether a TNF-induced increase in superoxide (O(2)(*)(-)) contributes to mitochondrial damage in the left ventricle (LV) by impairing respiratory complex I activity. We employed an electron paramagnetic resonance (EPR) method to measure O(2)(*)(-) and oxygen consumption in mitochondrial respiratory complexes, using an oxygen label. Adult male Sprague-Dawley rats were divided into four groups: control, TNF treatment (ip), TNF+ apocynin (APO; 200 micromol/kg bw, orally), and TNF+ Tempol (Temp; 300 micromol/kg bw, orally). TNF was injected daily for 5 days. Rats were sacrificed, LV tissue was collected, and mitochondria were isolated for EPR studies. Total LV ROS production was significantly higher in TNF animals than in controls; APO or Temp treatment ameliorated TNF-induced LV ROS production. Total mitochondrial ROS production was significantly higher in the TNF and TNF+ APO groups than in the control and TNF+ Temp groups. These findings suggest that TNF alters the cellular redox state, reduces the expression of four complex I subunits by increasing mitochondrial O(2)(*)(-) production and depleting ATP synthesis, and decreases oxygen consumption, thereby resulting in mitochondrial damage and leading to LV dysfunction.


Trimethoprim and the CYP2C8*3 allele have opposite effects on the pharmacokinetics of pioglitazone.
We studied the effects of the CYP2C8 inhibitor trimethoprim and CYP2C8 genotype on the pharmacokinetics of the antidiabetic pioglitazone. In a randomized crossover study, 16 healthy volunteers with the CYP2C8(*)1/(*)1 (n = 8), (*)1/(*)3 (n = 5), or (*)3/(*)3 (n = 3) genotype ingested 160 mg of trimethoprim or placebo twice daily for 6 days. On day 3, they ingested 15 mg of pioglitazone. The effects of trimethoprim on pioglitazone were characterized in vitro. Trimethoprim raised the area under the plasma pioglitazone concentration-time curve (AUC(0-infinity)) by 42% (p < 0.001) and decreased the formation rates of pioglitazone metabolites M-IV and M-III (p < 0.001). During the placebo phase, the weight-adjusted AUC(0-infinity) of pioglitazone was 34% smaller in the CYP2C8(*)3/(*)3 group and 26% smaller in the CYP2C8(*)1/(*)3 group than in the CYP2C8(*)1/(*)1 group (p < 0.05). Trimethoprim inhibited M-IV formation in vitro (inhibition constant 38.2 muM), predicting the in vivo interaction. In conclusion, drug interactions and pharmacogenetics affecting the CYP2C8 enzyme may change the safety of pioglitazone.


Generation of Oxtr cDNA(HA)-Ires-Cre Mice for Gene Expression in an Oxytocin Receptor Specific Manner.
The neurohypophysial hormone oxytocin (OXT) and its receptor (OXTR) have critical roles in the regulation of pro-social behaviors, including social recognition, pair bonding, parental behavior, and stress-related responses. Supporting this hypothesis, a portion of patients suffering from autism spectrum disorder have mutations, such as single nucleotide polymorphisms, or epigenetic modifications in their OXTR gene. We previously reported that OXTR-deficient mice exhibit pervasive social deficits, indicating the critical role of OXTR in social behaviors. In the present study, we generated Oxtr cDNA(HA)-Ires-Cre knock-in mice, expressing both OXTR and Cre recombinase under the control of the endogenous Oxtr promoter. Knock-in cassette of Oxtr cDNA(HA)-Ires-Cre consisted of Oxtr cDNA tagged with the hemagglutinin epitope at the 3' end (Oxtr cDNA(HA)), internal ribosomal entry site (Ires), and Cre. Cre was expressed in the uterus, mammary gland, kidney, and brain of Oxtr cDNA(HA)-Ires-Cre knock-in mice. Furthermore, the distribution of Cre in the brain was similar to that observed in Oxtr-Venus fluorescent protein expressing mice (Oxtr-Venus), another animal model previously generated by our group. Social behavior of Oxtr cDNA(HA)-Ires-Cre knock-in mice was similar to that of wild-type animals. We demonstrated that this construct is expressed in OXTR-expressing neurons specifically after an infection with the recombinant adeno-associated virus carrying the flip-excision switch vector. Using this system, we showed the transport of the wheat-germ agglutinin tracing molecule from the OXTR-expressing neurons to the innervated neurons in knock-in mice. This study might contribute to the monosynaptic analysis of neuronal circuits and to the optogenetic analysis of neurons expressing OXTR.


Relative response of populations of Escherichia coli and Salmonella enterica to exposure to thermal, alkaline and acidic treatments.
We evaluated the relative response of generic Escherichia coli (GEC), Shiga toxin-producing E. coli (STEC) and Salmonella enterica to heat, alkaline or acid treatments. GEC included strains from carcasses (n = 24) and trim (n = 25) at a small beef plant where no decontamination interventions are used and at a large plant where multiple decontamination interventions are used (carcass n = 25 and trim n = 25). STEC strains belonging to nine serogroups, included isolates from cattle (n = 53), beef (n = 16) and humans (n = 44). S. enterica strains belonging to 29 serotypes, included isolates from humans (n = 30), poultry (n = 26), pork (n = 10) and beef (n = 33). Strains were grown in Brain Heart Infusion (BHI) broth and subjected to the following treatments: 60 °C for 2 min, 5% lactic acid (pH 2.9) for 1 h at 4 °C, or NaOH (pH 11.0) for 2 h at 4 °C. Median log reductions of the GEC populations after heat, alkaline and acid treatment ranged from 2.3 to 3.8, 0.7 to 2.2 and 0.7 to 1.2 log CFU/mL, respectively. No statistically significant difference in reductions was observed between carcass GEC or trim GEC from the large or small plant, except for a greater reduction in trim GEC from the small plant. Median reductions of the STEC populations ranged from 3.3 to 3.5, 0.0 to 0.6, and 0.3 to 0.5 log CFU/mL after heat, alkaline and acid treatment, respectively. The median reductions were not dependent upon isolation source, except between STEC cattle and human isolates after alkaline treatment, where the reduction of the former was higher by 0.6 log unit. For the Salmonella populations, median log reductions ranged from 3.5 to 4.0, 1.7 to 2.4 and 3.7 to 4.1 log CFU/mL after heat, alkaline and acid treatment, respectively. The reductions were not isolation source related. The median log reductions were in the order GEC < STEC < Salmonella after heat treatment and STEC < GEC < Salmonella after alkaline or acid treatment. Overall, the relative response of GEC, STEC and Salmonella in the model system suggests that exposure to heat or pH-based decontamination interventions in meat plants is not associated with increased resistance among E. coli strains in these environments, and total E. coli counts on beef can be indicative of treatment efficacy for the control of Salmonella by heat, lactic acid and alkaline treatment and for the control of STEC subjected to heat.


[The effect of betain on biology and morphology of developmental stages of Eimeria acervulina in broiler chicks experimentally infected].
Purposing to investigate the betaine effect on biology and morphology of developmental stages of Eimeria acervulina, 420 broiler chicks Cobb were experimentally inoculated with 2 x 10(5) sporulated oocysts and housed in battery cages in a block design with five treatments and six replicates each, including a positive control, a group treated with salinomycin and growth promoter plus three levels of betaine as additive in the feed at 0.05, 0.10 and 0.15%. Measurements of oocysts, sporocysts and endogenous stages were performed as morphological parameters, while pre patent and patent periods and sporulation time were taken as biological parameters. Morphology was also associated with the mathematical constant Phi (1.618) to evaluate possible relationship. Betaine was able to cause modifications in both biology and morphology of oocysts and sporocysts, whereas it was weakly able to affect developmental stages based on trophozoites and macrogamonts measurements. According to the measures of sporocysts E. acervulina development was closely related to Phi.


The expression of miR-21 and miR-143 is deregulated by the HPV16 E7 oncoprotein and 17β-estradiol.
MicroRNAs (miRNAs) are a class of non-coding RNAs that negatively regulate their target mRNAs at a posttranscriptional level, thereby affecting crucial processes in cancer development. However, little is known about the molecular events that control expression of miRNAs in cervical cancer (CC). HPV16 E7 oncoprotein in conjunction with estrogen are sufficient to produce high grade cervical dysplasia and invasive cervical malignancies in a mouse model. In the present study, we determined the potential role that the E7 oncoprotein and 17β-estradiol (E2) play in the deregulation of miR-21 and miR-143 expression levels by these two risk factors. We found that, while the expression of miR-21 was upregulated and the expression of miR-143 was downregulated by the HPV16 E7 oncoprotein in vivo, and in vitro and that E2 treatment is also implicated in the deregulation of these important miRNAs in vivo. Sustained upregulation of miR-21 resulted in suppression of PTEN expression, and repression of miR-143 increased the mRNA and protein levels from Bcl-2. These results suggested that HPV type 16 E7 oncoprotein and E2 play an important role in regulating miR-21 and miR-143 expression. We have observed similar results in CC patients containing HPV16 sequences, suggesting that these miRNAs could serve as diagnostic biomarkers in CC. The present study highlights the roles of miRNAs in cervical tissue and implicates these important molecules in cervical carcinogenesis.


Resident Perception of a Newsletter's Impact on Residency Morale and Collegiality.
While several residency programs have created residency newsletters, no study has evaluated resident perception of a newsletter's impact. The objective of this study was to evaluate the impact of a newly implemented residency newsletter on resident morale and attitude toward fellow residents. At a Midwestern PGY1-3 emergency medicine residency program, a four-page monthly newsletter was implemented in April of 2005. The newsletter included features on residents, stories on residency events, and information on upcoming events. The newsletter was designed as a resident project in which residents contributed stories and photos. Content and editorial decisions were independent of residency faculty. Ten months after implementation of the newsletter, the program's residents were surveyed to assess the newsletter's impact on their morale and attitude toward fellow residents. They also reported their interest in participating as a formal newsletter staff and they provided their opinion on faculty oversight. The survey was conducted anonymously, was distributed in both paper and electronic forms, and was based on a five-point Likert scale (1-negative, 5-positive). Of the 37 eligible residents, 32 (86.5%) responded to the survey; 84.6% of PGY-3 residents, 83% of PGY-2, and 91.6% of PGY-1 residents participated. When asked to rate the newsletter's impact on their general morale, the mean rating for all residents was 4.6 (range 2-5, standard deviation 0.64, median 4). PGY-3 residents' mean rating was 4.7, PGY-2 mean was 4.5, and PGY-1 mean was 4.6. Residents were asked to rate the newsletter's impact on their attitudes toward fellow residents; the mean rating for all residents was 4.7 (range 3-5, standard deviation 0.53, median 4). PGY-3 residents' mean rating was 4.7, PGY-2 was 4.7, and PGY-1 was 4.6. When asked if they would be willing to contribute to the newsletter as part of a formal staff, 53% of residents responded "yes"; 27% of PGY-3, 60% of PGY-2, and 70% of PGY-1 answered "yes." Residents were queried as to whether they would like more faculty oversight of the newsletter; no residents (0%) responded "yes." 100% of residents (32/32) stated that they read the newsletter monthly. In a relatively large Midwestern PGY-1-3 emergency medicine residency program, nearly all residents perceived a monthly residency newsletter as having a positive impact on their general morale and on their attitudes toward fellow residents. Most junior residents were interested in joining a formal newsletter staff, and residents unanimously expressed their interest in maintaining the independent format of the newsletter. While results will vary across programs, a residency newsletter may be a relatively inexpensive means of improving resident morale and positively impacting residents' attitudes toward their colleagues.


Clinical efficacy of sclerotonyxis for acute angle-closure glaucoma with persistent high intraocular pressure.
The aim of the study was to investigate the clinical effectiveness and safety of sclerotonyxis in acute angle-closure glaucoma (ACG) with persistent high intraocular pressure (IOP). The clinical data of 50 eyes from 50 patients (mean age: 68.9±7.19 years) with acute ACG and persistently high IOP who were admitted to our department between January 2012 and January 2022 were retrospectively analyzed. Patients who were administered the maximum dose of systemic and topical anti-glaucoma drugs and still had an IOP of >40 mmHg 24 hours after admission underwent sclerotonyxis. After the IOP control, an individualized phase II treatment plan was designed according to the patient's ocular condition. Forty-eight patients showed improvement in their visual acuity 6 months postoperatively compared to their preoperative values. The mean IOPs were 54.84±7.82 mmHg and 21.34±7.81 mmHg 24 hours pre and postoperatively, respectively. The mean anterior chamber depth showed statistically significant differences pre and postoperatively (1.75±0.16 mm and 1.84±0.17 mm, respectively) (p<0.05). After IOP stabilized, four patients underwent YAG laser peripheral iridectomy, 18 underwent simple cataract phacoemulsification combined with intraocular lens (IOL) implantation, 21 underwent cataract phacoemulsification combined with IOL implantation and goniosynechialysis under a gonioscope, and 7 patients underwent combined surgery of glaucoma and cataract. The mean IOPs were 15.94±3.3 mmHg and 15.64±2.99 mmHg 1 week and 6 months after stage II surgery, respectively. Moreover, 42 eyes (84%) attained complete success and 8 eyes (16%) attained conditional success 6 months postoperatively. No serious complications, such as corneal endothelial decompensation, malignant glaucoma, vitreous or eruptive choroidal hemorrhage, and retinal detachment, were observed intraoperatively or postoperatively in both procedures. Sclerotonyxis can rapidly lower IOP, release the pupillary blockage, reconstruct the anterior chamber, and reduce systemic complications caused by long-term high-dose antiglaucoma drugs. Thus, it normalizes the IOP and provides a safe operating space for stage II surgery, effectively reducing complications in patients in a persistent high IOP state.


Investigation into the causes of aspirin resistance in healthy dogs.
Antiplatelet effects of acetylsalicylic acid (ASA, aspirin) may be poor in some individuals. Additionally, no method exists for predicting poor ASA response (resistance) in individual dogs. This study's main objective was to determine whether poor ASA response results from pharmacodynamic or pharmacokinetic causes. ASA concentrations causing 50% inhibition of platelet aggregation (in vitro IC50) were determined using whole blood collected from 21 drug-free healthy dogs to evaluate intrinsic sensitivity of platelets to ASA. Dogs were then administered ASA at 4 mg/kg once orally. Percent decrease in platelet aggregation from baseline, and plasma ASA and salicylic acid (SA) concentrations (expressed as AUC values) were measured for up to 3 hr. By 3 hr, 13/21 (62%) dogs showed >50% aggregation inhibition, while 8/21 (38%) dogs showed <50% inhibition. Aggregation inhibition values were negatively correlated with in vitro IC50 values (Rs = -0.49; p = 0.028) and positively correlated with ASA concentrations (Rs = 0.48; p = 0.03). Furthermore, ASA concentrations were strongly negatively correlated (Rs = -0.88; p < 0.001) with SA/ASA concentration ratios, an index of ASA metabolism to SA by esterase enzymes. Multiple linear regression analysis indicated that 59% (p < 0.001) of interindividual variability in aggregation inhibition was explained by in vitro IC50 values (29% of variability) and ASA concentrations (29% of variability). Consequently, poor in vivo ASA response in these dogs resulted from both pharmacodynamic (decreased platelet sensitivity) and pharmacokinetic (lower ASA concentrations) causes. Lower ASA concentrations may be explained by reduced bioavailability associated with higher esterase activities.


[Ocular injuries and childbirth].
Severe ocular traumatisms related to childbirth are rare and often subordinate to maneuvers with instruments. The aim of this study was to report on the different severe ocular injuries that might occur during childbirth and their possible consequences. There can be several of these ocular injuries. Since 1984, we have examined 11 cases of this type of traumatism. For each case, the childbirth circumstances, the affected side, the different injuries observed such as ocular, orbital, cranial and even cerebral lesions, and the results of the ophthalmological follow-up examinations were recorded. In most cases, lesions resulted from forceps traumatisms, and the injuries were corneal (vertical tears in the Descemet's membrane), retinal (hemorrhages), and orbital (e.g., the optical nerve and oculomotor nerve). These injuries, sometimes severe, must benefit from early and complete examination, possibly with general anesthesia, and long-term follow-up. Furthermore, a radiographic and clinical neurological examination is recommended to prevent any cerebral complication.


Elderly patients' and their informal caregivers' perceptions of care given: the study-control ward design.
This preliminary study is part of an ongoing action research project. Elderly patients (n = 45) and their informal caregivers (n = 147) completed a questionnaire. The purpose of this study was to evaluate the quality of care from both the patients' and their informal caregivers' points of view and to compare differences in perceived quality of care between study and control wards in different hospitals. Results indicated that the great majority of elderly patients were satisfied with the fulfillment of their needs. Informal caregivers evaluated the quality of care more critically than did the patients. Statistically significant differences were found between the control and the study wards in acute-care settings; however, differences between the wards in long-term care settings were non-significant. Nurses and researchers must better understand the needs of an increasing population of elderly patients. Informal caregivers are in a key position to help nursing professionals to cope with the future challenges of elderly people's care. Their perceptions must also be taken into account.


Women's health during mid-life survey: the use of complementary and alternative medicine by symptomatic women transitioning through menopause in Sydney.
To survey the extent of complementary and alternative medicine (CAM) use among women for the alleviation of menopausal symptoms. A total of 1,296 eligible women aged 45 to 65 years were recruited from three Sydney menopause clinics, general practice clinics, and government agencies between July 2003 and July 2004. Volunteers were invited to complete a 19-item questionnaire covering basic demographics, general health status, use of CAM therapies and products, use of pharmaceuticals, and sources of CAM advice. Of respondents, 53.8% had visited a CAM practitioner and/or used a CAM product during the past year, with 34% using a product only and 5% consulting a practitioner only. The most commonly visited practitioners were naturopaths (7.2%) and acupuncturists (4.8%), whereas the most popular products were soy (25.4%) and evening primrose oil (18.4%). Massage, chiropractic, and nutrition were rated the most effective therapies, and phytoestrogen tablets, evening primrose oil, and black cohosh were deemed the most effective products. Of the 59.9% of respondents currently using prescription or over-the-counter pharmaceuticals, 62.5% reported using CAM products during the past 12 months. Of CAM users 71% had informed their doctor about CAM use, whereas 26.4% of respondents reported their doctor had inquired about CAM use. CAM use by women to alleviate menopausal symptoms is common, with several therapies perceived to be effective. Although a significant proportion of women may use CAM in conjunction with pharmaceuticals, relevant communication between medical practitioners and patients remains inadequate and may expose the patient to potential drug-herb interactions.


Implementing an intensified antibiotic stewardship programme targeting daptomycin use in orthopaedic surgery: a cost-benefit analysis from the hospital perspective.
Hospital antibiotic stewardship (ABS) programmes offer several evidence-based tools to control prescription rates of antibiotics in different settings, influence the incidence of nosocomial infections and to contain the development of multi-drug-resistant bacteria. In the context of endoprosthetic surgery, however, knowledge of core antibiotic stewardship strategies, comparisons of costs and benefits of hospital ABS programmes are still lacking. We identified a high daptomycin use for the treatment of methicillin-sensitive staphylococcal infections as a potential target for our ABS intervention. In addition, we endorsed periprosthetic tissue cultures for the diagnosis of PJI. Monthly antibiotic use data were obtained from the hospital pharmacy and were expressed as WHO-ATC defined daily doses (DDD) and dose definitions adapted to local guidelines (recommended daily doses, RDD), normalized per 1000 patient days. The pre-intervention period was defined from February 2012 through January 2014 (24 months). The post-intervention period included monthly time points from February 2014 to April 2015 (15 months). For a basic cost-benefit analysis from the hospital perspective, three cost drivers were taken into account: (1) the cost savings due to changes in antimicrobial prescribing; (2) costs associated with the increase in the number of cultured tissue samples, and (3) the appointment of an infectious disease consultant. Interrupted time-series analysis (ITS) was applied. Descriptive analysis of the usage data showed a decline in overall use of anti-infective substances in the post-intervention period (334.9 vs. 221.4 RDDs/1000 patient days). The drug use density of daptomycin dropped by -75 % (51.7 vs. 12.9 RDD/1000 patient days), whereas the utilization of narrow-spectrum penicillins, in particular flucloxacillin, increased from 13.8 to 33.6 RDDs/1000 patient days. ITS analysis of the consumption dataset showed significant level changes for overall prescriptions, as well as for daptomycin (p < 0.001) and for narrow-spectrum penicillins (p = 0.001). The total costs of antibiotic consumption decreased by an estimated € 4563 per month (p < 0.001), and around 90 % of these savings were linked to a decrease in daptomycin consumption. Overall, the antibiotic stewardship programme was beneficial, as monthly cost savings of € 2575 (p = 0.005) were achieved. In this example of large endoprosthetic surgery department in a community-based hospital, the applied hospital ABS programme targeting daptomycin use has shown to be feasible, effective and beneficial compared to no intervention.


Reduction of T Cells and Hsa-miR150-5p in Female Canoeing Athletes: Preliminary Evidence Between Exercise Training and Immune.
Xiao, F, Yang, Y, Xiao, L, Xia, Z, Wang, L, Yang, K, and Wang, S. Reduction of T cells and hsa-miR150-5p in female canoeing athletes: Preliminary evidence between exercise training and immune. J Strength Cond Res 36(11): e106-e113, 2022-This article aims to reveal the alteration of immune profile in teenage canoeing athletes, by which applies a clue for regulation of exercise on human immune. Thirty-one teenagers of female canoeing athletes and age-matched subjects participated in this research. Peripheral leukocytes' microRNAs (miRNAs) were analyzed using Agilent human microRNA 2.0 and gene software. The miRNA candidates were quantified by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). The percentages of various lymphocytes were tested using flow cytometry. There were 6 miRNAs (hsa-miR150-5p, 31-5p, 3659, 4419a, 650, and 8485) lower in canoeing athletes, and the reduction of miR-150 was identified by RT-qPCR ( p = 0.021). Canoeing athletes had lower percent of CD3 + T cells than the subjects with no exercise training had ( p < 0.001), but the ratio of CD4 + to CD8 + and the percent of CD4 + T cells and CD8 + T cells showed no significant difference between these 2 groups. T cells and hsa-miR150-5p are sensitive to the long-time heavy exercise training, and the exercise for winning competition regulates the immune system by inhibiting T cells and hsa-miR150-5p.


Measurements of body fat in Indonesian adults: Comparison between a three-compartment model and widely used methods.
Body composition was assessed in Indonesian male (n = 18) and female (n = 23) students using densitometry (underwater weighing), deuterium oxide dilution, skinfold thickness measurements, bioelectrical impedance analysis (BIA) and a prediction equation based on the body mass index. From body density and total body water percentage body fat (BF%) was calculated using a three-compartment body composition model. Percentage body fat obtained by this three-compartment model was regarded as the reference value and BF% obtained by the single methods were compared with this value. Mean differences (± SD) in BF% from the threecompartment model minus the single methods were -1.1 ± 2.1 for densitometry, +1.1 ± 1.6 for deuterium oxide dilution, +1.3 ± 2.8 for skinfold thickness measurement, +2.8 ± 4.3 for BIA and +3.4 ± 4.8 for body mass index in males. In females these values were +0.1 ± 1.7, +0.2 ± 1.4, +3.6 ± 3.3, +3.6 ± 2.4 and +8.7 ± 2.0 BF%, respectively. Correlation coefficients between different methods were high and significant (P < 0.05 in males, P < 0.001 in females). This study shows that the single predictive methods have considerable mean and individual biases compared with the three-compartment model and all predictive methods underestimated body fat in the studied subjects. It is concluded that the development of population-specific prediction formulas may be necessary.


Multivalent Traptavidin-DNA Conjugates for the Programmable Assembly of Nanostructures.
Here, we explore the extended utility of two important functional biomolecules, DNA and protein, by hybridizing them through avidin-biotin conjugation. We report a simple yet scalable technique of successive magnetic separations to synthesize traptavidin-DNA conjugates with four distinct DNA binding sites that can be used as a supramolecular building block for programmable assembly of nanostructures. Using this nanoassembly platform, we fabricate several different plasmonic nanostructures with various metallic as well as semiconductor nanoparticles in predetermined ways. We also use the platform to construct dendrimer nanostructures using valency-controlled traptavidin-DNA conjugates in a programmable manner. These results suggest that our protein-DNA supramolecular building blocks would make a significant contribution to the assembly of multicomponent and complex nanostructures for numerous contemporary and future applications from molecular imaging to drug delivery.


Synthetic peptide homologous to the envelope proteins of retroviruses shares a cross-reacting epitope with the CD4 receptor.
A synthetic peptide (CKS-17) homologous to a highly conserved region of the retroviral transmembrane protein p15E was tested for its effect on receptor expression on monocytes. The CKS-17 amino acid sequence is present in several retroviruses including human T-cell lymphotropic virus types I and II and human immunodeficiency virus. The CKS-17 peptide has been previously shown to inhibit monocyte superoxide production, natural killer cell activity, polyclonal B-cell activation, and monocyte-mediated killing by inactivation of interleukin-1. In this study, we demonstrated that the anti-CD4 monoclonal antibody OKT4 binds strongly in vitro to CKS-17-treated human blood monocytes, whereas other antibodies tested were not reactive. This observed binding was the result of direct interaction of OKT4 antibody with the CKS-17 peptide. Moreover, a partial homology was found in amino acid sequence analysis of the CD4 epitope and the CKS-17 peptide.


Toxicological analysis of low-nicotine and nicotine-free cigarettes.
Low-nicotine and nicotine-free cigarettes are commercially available under the brand-name Quest. Some consumers may believe that these are safer cigarettes, and they may smoke more cigarettes or inhale more smoke to compensate for low nicotine yields. Thus, we have studied the toxicological effects of these two cigarettes and compared them with the Kentucky reference cigarette 2R4F. Also, the availability of nicotine-free cigarettes allows for the assessing the role of nicotine in cigarette smoke. In addition to nicotine, some tobacco-specific nitrosamines, aldehydes, and volatile organic compounds were also reduced in the Quest cigarettes compared to the 2R4F. However, aromatic amines were higher in the nicotine-free compared with low nicotine cigarettes. The Ames test revealed that cigarette smoke condensates from the nicotine-free (CSC-F), low nicotine (CSC-L) and 2R4F (CSC-R) cigarettes had a similar mutagenic potency. Exposure to any CSC caused a similar dose-dependent LDH leakage from normal human bronchial epithelial cells. However, CSC-F had more inhibitory effects on the cell growth than CSC-L and CSC-R. Adding nicotine to the CSC-F attenuated this inhibition. Both Quest CSCs decreased gap junction intercellular communication and caused cell cycle arrest. CSC exposure increased cytoplasmic nucleosomes, sub-G1/G0 population and apoptotic comet tails. Proapoptotic protein Bax increased independent of p53 induction after exposure to CSC-F. In conclusion, these studies are not consistent with a perception that low-nicotine or nicotine-free cigarettes may have less toxicity in human cells. Nicotine, as it exists in CSC, attenuates cytotoxicity possibly in part through inhibition of apoptotic pathways.


The cyclic peptide G4CP2 enables the modulation of galactose metabolism in yeast by interfering with GAL4 transcriptional activity.
Genetically-encoded combinatorial peptide libraries are convenient tools to identify peptides to be used as therapeutics, antimicrobials and functional synthetic biology modules. Here, we report the identification and characterization of a cyclic peptide, G4CP2, that interferes with the GAL4 protein, a transcription factor responsible for the activation of galactose catabolism in yeast and widely exploited in molecular biology. G4CP2 was identified by screening CYCLIC, a Yeast Two-Hybrid-based combinatorial library of cyclic peptides developed in our laboratory. G4CP2 interferes with GAL4-mediated activation of galactose metabolic enzymes both when expressed intracellularly, as a recombinant peptide, and when provided exogenously, as a chemically-synthesized cyclic peptide. Our results support the application of G4CP2 in microbial biotechnology and, additionally, demonstrate that CYCLIC can be used as a tool for the rapid identification of peptides, virtually without any limitations with respect to the target protein. The possible biotechnological applications of cyclic peptides are also discussed.


Central nervous system abnormalities in migraine.
Migraine is associated with structural and functional CNS changes, for example, ictal hyperalgesia and allodynia and interictal neural excitation. Structural abnormalities, most notably white matter changes, occur in greater prevalence in migraineurs (16 - 40%). Several studies have examined the neuropsychological correlates of migraine and/or white matter abnormalities. These studies suggest mild, interictal dysfunction in migraineurs. More research is needed to correlate migraine severity, frequency and/or treatment with neuropsychological testing. Additional studies should: identify interictal cognitive changes; clarify the contribution to long-term cognitive changes from migraine genotype, sequelae of repeated pain episodes or their treatment and the consequences of co-morbid vascular disease; and include cognitive measures as secondary end points in clinical trials.


Gene deletions in Mycobacterium bovis BCG stimulate increased CD8+ T cell responses.
Mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host's immune response. It has been suggested that mycobacteria may contain genes that reduce the host's ability to elicit CD8(+) T cell responses. We screened 3,290 mutant Mycobacterium bovis bacillus Calmette Guerin (BCG) strains to identify genes that decrease major histocompatibility complex (MHC) class I presentation of mycobacterium-encoded epitope peptides. Through our analysis, we identified 16 mutant BCG strains that generated increased transgene product-specific CD8(+) T cell responses. The genes disrupted in these mutant strains had disparate predicted functions. Reconstruction of strains via targeted deletion of genes identified in the screen recapitulated the enhanced immunogenicity phenotype of the original mutant strains. When we introduced the simian immunodeficiency virus (SIV) gag gene into several of these novel BCG strains, we observed enhanced SIV Gag-specific CD8(+) T cell responses in vivo. This study demonstrates that mycobacteria carry numerous genes that act to dampen CD8(+) T cell responses and suggests that genetic modification of these genes may generate a novel group of recombinant BCG strains capable of serving as more effective and immunogenic vaccine vectors.


Payment policy and the growth of Medicare Advantage.
This paper reviews recent trends in Medicare Advantage, examining program costs, access to plans, enrollment, plan bids, and benchmarks. We find that current policy has favored the growth of particular types of plans. Bid data show that plans are paid, on average, 113 percent of what expenditures would have been under the traditional Medicare program. Although some of the plan payments are used to finance extra benefits for enrollees, paying plans at higher than fee-for-service levels could affect the sustainability of the Medicare program and result in increased costs for all taxpayers and beneficiaries.


The Renaissance of Metal-Pyrimidine Nucleobase Coordination Chemistry.
The significance of metal ions for the function and properties of DNA and RNA, long seen primarily under biological aspects and medicinal uses, has recently gained a renewed momentum. This is a consequence of the advent of novel applications in the fields of materials science, biotechnology, and analytical sensor chemistry that relate to the designed incorporation of transition metal ions into nucleic acid base pairs. Ag(+) and Hg(2+) ions, binding to pyrimidine (pym) nucleobases, represent major players in this development. Interestingly, these metal ions were the ones that some 60 years ago started the field! At the same time, the mentioned metal ions had demonstrated a "special relationship" with the pym nucleobases cytosine, thymine, and uracil! Parallel work conducted with oligonucleotides and model nucleobases fostered numerous significant details of these interactions, in particular when X-ray crystallography was involved, correcting earlier views occasionally. Our own activities during the past three to four decades have focused on, among others, the coordination chemistry of transition and main-group metal ions with pym model nucleobases, with an emphasis on Pt(II) and Pd(II). It has always been our goal to deduce, if possible, the potential relevance of our findings for biological processes. It is interesting to put our data, in particular for trans-a2Pt(II) (a = NH3 or amine), into perspective with those of other metal ions, notably Ag(+) and Hg(2+). Irrespective of major differences in kinetics and lability/inertness between d(8) and d(10) metal ions, there is also a lot of similarity in structural aspects as a result of the preferred linear coordination geometry of these species. Moreover, the apparent clustering of metal ions to the pym nucleobases, which is presumably essential for the formation of nanoclusters on oligonucleotide scaffolds, is impressively reflected in model systems, as are reasons for inter-nucleobase cross-links containing more than a single metal ion. The present understanding of these interrelationships is a consequence of intensive research carried out during the last 60 years by numerous laboratories. For space restrictions in this Account, it was impossible to adequately highlight the valuable contributions of all of the researchers in the field of metal-pym nucleobase interactions. Explicitly this refers to colleagues not cited in the references, e.g., R. Stuart Tobias, Robert Bau, R. Bruce Martin, Colin J. L. Lock, Katsuyuki Aoki, Helmut Sigel, and Michael J. Clarke, among others.


Skin conductance responses in patients sedated with midazolam or propofol.
We have measured the skin conductance response under resting conditions and to innocuous auditory stimuli in 45 patients receiving midazolam (group M), propofol (group P) or no sedative drug (group ND) before minor hand surgery under local anaesthesia. Administration of the sedative drugs was titrated to the end-point of slurring of speech and ptosis. The mean dose of midazolam was 0.06 (SD 0.01) mg kg-1 and the mean infusion rate of propofol was 2.2 (0.39) mg kg-1 h-1. Subjective ratings of anxiety and sedation were measured using visual analogue scales. These were similar in groups M and P and significantly different from those reported by group ND (P = 0.001-0.005). However, measures of skin conductance in group M were significantly lower than in group P (P = 0.002-0.013) and group ND (P = 0.004-0.016). These measures were similar in groups P and ND. Skin conductance measures were related significantly to anxiety scores only in groups M and ND (P < 0.05). We conclude that skin conductance is not a non-specific index of sedative-anxiolytic action and therefore is not useful in comparative studies of anxiolytic drugs that exert their effects by different pharmacological mechanisms.


Engineered phytases for emerging biotechnological applications beyond animal feeding.
Phytases are important industrial enzymes able to catalyze the release of up to six phosphates from phytate in a stepwise hydrolysis reaction. Phytases are almost exclusively used as a feed supplement. However, phytases are also used in human nutrition, food processing, non-food industrial products, and emerging applications like enzymatic phosphate recovery from renewable resources. Phytate, the main phosphorus storage form in seeds, and its hydrolysis products act as a chelator and reduce protein and mineral bioavailability in intestinal absorption. Full phosphate hydrolysis from the common storage compound phytate remains a challenge. Phytate hydrolysis patterns of tailored phytases and their protein engineering campaigns are discussed. The aim of our review is to give an overview on developed and emerging application areas (animal nutrition, food processing, and environmental resource management) and thereby generate an awareness for the importance of phosphorus stewardship in a circular bioeconomy. Emphasis will be given to processes using organic-bound phosphorus and related recycling strategy of this valuable resource. In detail, the main challenge in designing phytases to completely hydrolyze phosphate from phytate to inositol and the need for engineering campaigns to broaden their industrial use are described.


Full-endoscopic technique for anterior cervical discectomy and interbody fusion: 5-year follow-up results of 67 cases.
With minimally invasive technique becoming more popular, endoscopic operations such as arthroscopy or laparoscopy have become the standard of care in several other areas. In this study, we evaluated the 5-year follow-up outcomes of anterior cervical (Ahn et al. in Photomed Laser Surg 23:362-368, 2005) discectomy and interbody fusion (ACDF) performed via endoscopic approach. Sixty-seven patients who underwent anterior cervical discectomy and cage fusion performed using endoscopic technique were followed for at least 5 years. We reviewed the clinical and radiographic records of these patients. The postoperative radiographic measures accessed were the anterior intervertebral height (AIH) and the lordosis angle (LDA). Clinical outcomes were determined using the previously validated Japanese Orthopaedic Association (JOA) and the pain visual analog scale (VAS). Patients included had a minimal follow-up period of 5 years and based on the outcomes criteria (JOA, VAS), 86.6% of patients reported excellent or good results. The AIH increased on average 18.7% of the original height (p < 0.01), and the LDA were more physiologic at final follow-up. Of the 67 cases, there was no segmental instability, and the bone fusion rate was 100%. One patient required revision open ACDF due to adjacent segment disc herniation 6 years postoperatively. There were no intraoperative complications, dysphasia or esophageal injury in this study group. It indicated endoscopic technique for ACDF can obtain satisfactory results in patients with cervical disc herniation, cervical myelopathy, or radiculopathy. Compared with a traditional approach, this technique may be associated with less morbidity while improving cosmesis and postoperative recovery. Prospective randomized control trials are needed to directly compare these two procedures.


Ultrastructural localization of cyclic adenosine 3',5'-monophosphate-dependent protein kinase after adrenocorticotropin stimulation in adrenal cortical tumor cells.
To increase our knowledge of the molecular details of peptide hormone action, a specific immunogold staining procedure for the ultrastructural localization of cAMP-dependent protein kinase regulatory (RI) and catalytic (C) subunits was used in Y-1 adrenal cortical tumor cells. The Y-1 adrenal cell responds to ACTH (40 mU/ml) with a decrease in cell division and an increase in steroid production. Corresponding to the decrease in rate of cell division and the increase in steroid production, there was a 2-fold increase in both nuclear and cytoplasmic localization of the C subunit after 60-min ACTH (40 mU/ml) treatment of the culture. The amount of immunogold staining in the adrenal tumor cells after localization with antiserum of the RI subunit decreased after 60-min ACTH (40 mU/ml) stimulation. A 2-fold decrease in labeling in the cytoplasm and nucleus was observed for the RI subunit. The loss of RI subunit from the soluble fraction of the cytoplasm of the cell or an alteration of this RI subunit is suggested by this investigation. Since there was no increase in the RI subunit in the nuclear compartment, a loss of RI subunit from the cytoplasm into the nucleus seems unlikely. The observed immunogold changes in the C subunit after ACTH treatment correspond to the reported changes observed with light microscopic techniques with a fluorescein-coupled inhibitor as a probe for the localization of free C. The immunogold technique allows for the ultra-structural identification and quantification of nuclear as well as the cytoplasmic sites of cAMP-dependent protein kinase after hormonal stimulation. These results support the proposed role of protein kinase as a mediator of the ACTH response.


[Neural sarcoidosis in children. A case report].
A case of cerebral sarcoidosis of fortuitous discovery is reported in an adolescent. Neurosarcoidosis is exceedingly rare in the pediatric age groups. Clinical manifestations are widely variable and nonspecific, making diagnosis difficult in patients without extraneurologic involvement. The mainstay of management is early, prolonged corticosteroid therapy. Outcome varies with location of the lesions.


[Better care and lower costs through registries; a first step to reimbursement based on outcome].
We have recently shown that costs of surgical treatment for colorectal carcinoma differ greatly between various patient groups in the Netherlands. Those cost-differences could mostly be explained by the fact that high-risk patients have a greater risk of complications, which generate higher hospital costs. Hospitals with a high-risk population, for instant tertiary referral centres, spend more than hospitals that treat low-risk patients. Currently reimbursement however is not geared to risk differences. In this article we investigate this shortcoming of the current reimbursement system and discuss how a differential rewarding - in which reimbursement is aligned with the patient's risk profile - could serve as a tool to further quality improvement in healthcare. Current clinical registries may provide the necessary details of patient characteristics for risk profiling and may also contribute to the following goal: reimbursement based on the quality of delivered care.


Hematomas and limb skeletal malformations in chicken embryos following exposure to 5-fluoro-2-deoxyuridine.
Vascular injury or interruption may play a role in vertebrate limb teratogenesis. Since 5-fluoro-2'-deoxyuridine (FdU) can cause vascular injury in the murine limb and skull prior to the appearance of skeletal malformations in these structures, we studied the effects of this chemical on skeletal development in the chick embryo and noted any vascular injury. The yolk sacs of day three chick embryos (Hamburger and Hamilton states 17-19) were injected with solutions of vary concentrations of FdU in saline. The embryos developed until the 10th day of incubation when they were fixed for study. Uninjected, saline injected, and sham injected control embryos were similarly fixed. Upon gross inspection, frequent diffuse and saccular hematomas, as well as fluid-filled blisters, were noted in the limbs of embryos treated with FdU. After the embryos were fixed and cleared, and the skeletons stained, significant skeletal malformations were observed in these limbs. Bony elements of both the upper and lower limbs were affected in at least some of the embryos. The combination of FdU-induced hematomas and blisters with associated skeletal malformations in the same regions of some embryos suggests a relationship between these phenomena.


Model of radiation transmittance by inorganic fouling on UV reactor lamp sleeves.
The efficacy of UV disinfection of water depends on the ability of radiation to pass from UV lamps through the quartz sleeves that encase them; the accumulation of metal-containing foulants on sleeve surfaces inhibits disinfection by absorbing radiation that would otherwise be available for inactivation. In a series of experiments, the composition and quantity of sleeve foulants were studied relative to water chemistry and sleeve transmittance. Findings indicate that iron and calcium dominate fouling, with elevated fouling activity by iron, aluminum, manganese, and zinc. A regression-based modeling approach was used to characterize and quantify the effects of foulant metals on UV absorbance. The molar extinction coefficient for iron was found to be more than 3 times greater than that of calcium. Iron's relatively high activity in fouling reactions, elevated capacity to absorb UV, and reduced solubility under oxidizing conditions makes it a fouling precursor of particular concern, with respect to potential for sleeve fouling in UV reactors.


Punctate midline myelotomy: a minimally invasive procedure for the treatment of pain in inextirpable abdominal and pelvic cancer.
The midline of the dorsal column contains a pathway that may be more important for transmitting visceral nociceptive signals than the spinothalamic tract. Punctate midline myelotomy, a neuroablative operation with the intent of interrupting the midline of the dorsal column, has demonstrated efficacy in the treatment of otherwise intractable abdominal and pelvic cancer pain. The indications, technical procedure, outcomes, and complications of all published clinical studies of punctate midline myelotomy are reviewed. The lesion level of the spinal cord and the depth of the incision are discussed, with the focus on the feasibility of this technique.


Introduction of a prescribing ward round to reduce prescribing errors on a paediatric intensive care unit.
Our paediatric intensive care unit (PICU) performs active surveillance for prescribing errors and detects a mean of 1.66 with an SD of 0.18 total prescription errors per occupied bed day. The primary aim of this project was to reduce the number of prescribing errors in PICU. The secondary aims were to improve the workflow in the unit and reduce the time staff spent on medication queries/prescribing. We introduced a daily multidisciplinary prescribing round to our PICU. Prescribing errors reduced, with the mean number of total prescription errors per bed day falling from 1.66 (0.18) to 1.19 (0.13), the mean number of clinical prescription errors per bed day falling from 0.46 (0.09) to 0.3 (0.07), and the mean number of non-clinical prescribing errors per bed day falling from 1.12 (0.15) to 0.67 (0.1). Forty-eight staff responded to the survey, 39 of whom had been directly involved in the rounds. The majority (37 of 39; 95%) said the prescribing round reduced the overall time they spent on prescribing/medication queries during their shift, and 9 of 10 (90%) prescribers said that they were interrupted fewer times for medication queries while doing other tasks. Almost all (47 of 48; 98%) said that they thought the prescribing ward round should continue. Introduction of a prescribing round with senior medical and pharmacist involvement was associated with a reduction in prescribing errors as well as reduction in the overall time staff spent on medication queries and prescribing. The round was well received by staff, with 98% wanting it to continue.


Effect of Fluoride Varnish on Enamel Remineralization in Anterior Teeth with Molar Incisor Hypomineralization.
The objective of this study was to investigate the effect of fluoride varnish on remineralization of anterior teeth affected by Molar-Incisor Hypomineralization (MIH) by means of Quantitative Light-Induced Fluorescence- QLF. Fifty-one healthy 9 - 12- year-old children were selected according to different clinically diagnosed levels of MIH, proposed by the European Academy of Pediatric Dentistry (2003) (considering the most severe lesion per patient, n= 51 lesions), and randomly divided into two groups: (1) four applications of 5% NaF varnish, with one-week interval, and (2) usual home care- control. At each visit, the mean change in fluorescence and area of lesion were measured by QLF. The data were analyzed by repeated measures ANOVA and Tukey's test. All patients showed enamel alterations in first permanent molars and incisors, frequently with two molars affected by MIH (41.1%). There was no statically significant difference in the mean of fluorescence and area of lesion between groups over the studied time. We observed no favorable effect on the remineralization of MIH lesions in anterior teeth after four applications of fluoride varnish.


Postural responses to vibration of neck muscles in patients with idiopathic torticollis.
Vibration of the dorsal muscles of the neck, simulating lengthening, in standing man causes a visible forwards tilt of the body shown on posturography as a tonic sagittal sway deviation. According to the theory that posture is organized with respect to a 'body schema' this deviation is a result of an interpretation of the concurrent neck afferent and vestibular signals. Considering the hypothesis that neck afferent signals may be misinterpreted in patients with spasmodic torticollis (ST) causing abnormal postural responses, we recorded body sway induced by unilateral dorsal neck muscle vibration in 22 idiopathic ST patients (19 treated with botulinum toxin) during upright stance with eyes closed. Comparison groups were 19 normal subjects and 11 patients with bilateral loss of vestibular function (labyrinthine defective, LD) in whom neck afference should be intact. Both treated and untreated ST and LD patients had absent or diminished sway deviations. When sway deviation did occur, it was sagitally oriented as with normal subjects and unrelated to ST head turns. In most ST and LD patients, neck vibration induced neck extension, an effect which is observed in normal subjects only if the torso is retrained. The results suggest that neck proprioceptive input retains local postural functions in ST, however, it is relatively ignored in the context of the whole body postural control and spatial orientation. The mild disorders of vestibular function reported in torticollis patients may be due to an inability to calibrate vestibular signals by reference to corroborative signals from neck proprioception.


MiR-206 controls the phenotypic modulation of pulmonary arterial smooth muscle cells induced by serum from rats with hepatopulmonary syndrome by regulating the target gene, annexin A2.
Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver disease that is characterised by intrapulmonary vascular dilatation (IPVD) and arterial hypoxemia. Pulmonary vascular remodelling (PVR) is an important pathological feature of HPS, but the potential mechanisms underlying PVR remain undefined. Recent findings have established the essential role of changes in Annexin A2 (ANXA2) in controlling the phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs) in PVR associated with HPS. However, the mechanism by which upstream signalling regulates ANXA2 is unclear. In the present study, computational analysis was used to predict which miRNA might target the 3´-untranslated region (3´-UTR) of the ANXA2 mRNA. Real-time PCR and western blotting were performed to study the level of correlation between ANXA2 and the differentiation marker with the predicted miRNAs in PASMCs stimulated with serum from normal rats or those with HPS. Functional analysis of the miRNA and a luciferase reporter assay were performed to demonstrate that the predicted miRNA suppressed ANXA2 expression by directly targeting the predicted 3´-UTR site of the ANXA2 mRNA. Computational analysis predicted that miR-206 would target the 3´-UTR of ANXA2 mRNA. In HPS rat serum-stimulated PASMCs, the expression of miR-206 displayed an inverse correlation with ANXA2, while a positive correlation was observed with the phenotypic marker smooth muscle α-actin (SM α-actin). The miRNA functional analysis and luciferase reporter assay demonstrated that miR-206 effectively downregulated the expression of ANXA2 by binding to the 3´-UTR of the ANXA2 mRNA. Consistently, miR-206 effectively inhibited the HPS rat serum-induced phenotypic modulation and proliferation, while these effects were reversed in ANXA2-overexpressing PASMCs. This study demonstrates that miR-206 inhibits the HPS rat serum-induced phenotypic modulation and proliferation in PASMCs by down-regulating ANXA2 gene expression.


[Adverse effects of antiretroviral therapy. Aspects of pathogenesis].
Highly active antiretroviral therapy has resulted in remarkable reduction of morbidity and mortality of HIV infection. With increasing duration of therapy metabolic alterations such as hyperlipidemia, diabetes mellitus type 2 and lipodystrophy are encountered which considerably reduced quality of life for the patients. These adverse events are most likely due to protease inhibitors and nucleoside analogues with synergistic effects. The pathogenesis is related to metabolic alterations of the adipocytes with cellular insulin resistance and enhanced apoptosis of these cells caused by adipocytic cytokines such as adiponectin, leptin, TNF-alpha and interleukin 2. Switch of therapy regimens with elimination of the most suspicious substances and certain protease inhibitors can lead to improvement of deranged metabolism. Also symptomatic therapy is possible to cope with hyperlipidemia and diabetes, although no effective treatment is available to reverse already existing lipodystrophy. Our knowledge about the pathogenesis of these alterations might lead to new concepts and causal therapy in the future.


Serial Analysis of Gene Expression: Applications in Human Studies.
Serial analysis of gene expression (SAGE) is a powerful tool, which provides quantitative and comprehensive expression profile of genes in a given cell population. It works by isolating short fragments of genetic information from the expressed genes that are present in the cell being studied. These short sequences, called SAGE tags, are linked together for efficient sequencing. The frequency of each SAGE tag in the cloned multimers directly reflects the transcript abundance. Therefore, SAGE results in an accurate picture of gene expression at both the qualitative and the quantitative levels. It does not require a hybridization probe for each transcript and allows new genes to be discovered. This technique has been applied widely in human studies and various SAGE tags/SAGE libraries have been generated from different cells/tissues such as dendritic cells, lung fibroblast cells, oocytes, thyroid tissue, B-cell lymphoma, cultured keratinocytes, muscles, brain tissues, sciatic nerve, cultured Schwann cells, cord blood-derived mast cells, retina, macula, retinal pigment epithelial cells, skin cells, and so forth. In this review we present the updated information on the applications of SAGE technology mainly to human studies.


Rarities in the catheterization Lab. A strange type of single coronary artery.
The single coronary artery, a rare but well described coronary artery anomaly, is considered potentially dangerous. A case of a 71-year old woman, suffering from a moderate arterial hypertension and frequent episodes of atypical chest pain is described. The woman was found to have a strange type of single coronary with hypoplastic circumflex coronary artery, difficulty classifiable as a Lipton R-II A single coronary artery. The anatomical features and classification criteria of the case are also described.


A descriptive study of adherence to lifestyle modificationfactors among hypertensive patients.
Healthy life style recommendations (e.g., physical activity, healthy diet, and decreased cholesterol levels) play an important role in controlling blood pressure (BP). This study aimed to assess lifestyle modification factors among patients diagnosed with hypertension. A descriptive-survey design was used. Data were collected using four questionnaires; one was the Beliefs about Medication questionnaire (BMQ) and the rest were developed to collect data about demographic and clinical characteristics and lifestyle modification factors. In total 312 questionnaires were completed. The results revealed that our participants did not follow the healthy lifestyle recommendations; for example, the mean blood sugar (BS) level, body mass index (BMI), and cholesterol levels were 155 mg/dL (standard deviation (SD) = 71.9), 29 kg/m2 (SD = 5.4), and 197 mg/dL (SD = 86.6), respectively. A significant correlation was shown between age and BP (P = 0.000). Increase in diastolic BP (DBP) correlated with a significant increase in cholesterol level (P = 0.002) and BMI (P = 0.006). Our study showed that somewhat hypertensive patients in Jordan did not follow a healthy lifestyle. Therefore, urgent action by addressing behavioral risk factors has a positive impact on preventing and controlling hypertension.


Proton-number fluctuation as a signal of the QCD critical end point.
We argue that the event-by-event fluctuation of the proton number is a meaningful and promising observable for the purpose of detecting the QCD critical end point in heavy-ion collision experiments. The long range fluctuation of the order parameter induces a characteristic correlation between protons which can be measured. The proton fluctuation also manifests itself as anomalous enhancement of charge fluctuations near the end point, which might be already seen in existing data.


Photoactive mitochondria: in vivo transfer of a light-driven proton pump into the inner mitochondrial membrane of Schizosaccharomyces pombe.
The light-driven proton pump bacteriorhodopsin (bR) from Halobacterium salinarium has been genetically transferred into the inner mitochondrial membrane (IM) of the eukaryotic cell Schizosaccharomyces pombe, where the archaebacterial proton pump replaces or increases the proton gradient usually formed by the respiratory chain. For targeting and integration, as well as for the correct orientation of bR in the IM, the bacterioopsin gene (bop) was fused to signal sequences of IM proteins. Northern and Western blot analysis proved that all hybrid gene constructs containing the bop gene and a mitochondrial signal sequence were expressed and processed to mature bR. Fast transient absorption spectroscopy showed photocycle activity of bR integrated in the IM by formation of the M intermediate. Experiments with the pH-sensitive fluorescence dye 2',7'-bis(2-carboxyethyl)-5 (and -6)-carboxyfluorescein revealed bR-mediated proton pumping from the mitochondrial matrix into the intermembrane space. Glucose uptake measurements under anaerobic conditions showed that yeast cells containing photoactive mitochondria need less sugar under illumination. In summary, our experiments demonstrate the functional genetic transfer of a light energy converter to a naturally nonphotoactive eukaryotic organism.


In vitro testing of surface thrombogenicity using the thrombelastograph.
Synthetic surfaces can be assessed for their ability to promote or inhibit whole blood coagulation with improved accuracy using a new protocol developed for the Thrombelastograph instrument. Results obtained from the analysis of the hydrodynamic state of blood clotting in Thrombelastograph chambers have enabled a quantitative interpretation of the output of this instrument to be made. The thrombogenic properties of a segmented polyurethane and a polydimethyl siloxane are compared with a preparation of reconstituted elastin. It is seen that a four-fold delay in clotting time is exhibited by reconstituted elastin when it is compared with other biomedical synthetic materials tested.


Importance of characterizing growth trajectories.
In the era of the obesity epidemic in children, characterizing childhood growth trajectories (weight, length/height, or body mass index/weight for length) is becoming essential for surveillance. Clinicians routinely use growth curves to identify abnormal growth trajectories. Clinical epidemiologists are interested in both the determinants of growth and the consequences of certain patterns of growth on later health and diseases. Characterizing growth trajectories is also helpful to predict future growth based on past growth and might be useful in the future to compare the impact of various interventions.


Difficulties in the diagnosis of pseudoachalasia.
We undertook this study to determine the utility of various clinical findings and tests in the diagnosis of pseudoachalasia. We reviewed the clinical, endoscopic, esophagographic, CT, and manometric findings of five patients with pseudoachalasia of malignancy. These patients were identified from our large group of 206 patients with manometrically diagnosed achalasia who were seen over the past 8 yr. For each pseudoachalasia patient, the two consecutively seen patients with idiopathic achalasia were chosen to comprise a control group. The pseudoachalasia patients, as compared to the control group, had shorter duration of dysphagia (9.6 +/- 8.6 months vs 54.3 +/- 44.2 months, p < 0.05). They had similar weight loss (15.6 +/- 12.8 lbs vs 14.3 +/- 18.4 lbs, p = NS), but weight loss/time, where time is months of symptoms, was greater in the pseudoachalasia group (1.8 +/- 1.8 lbs/month vs 0.5 +/- 0.5 lbs/month, p < 0.05). There was, however, substantial overlap between the groups in all these parameters. Barium esophagography failed to reveal cancer in any of the pseudoachalasia patients. There was difficult passage of the endoscope through the gastroesophageal junction in all patients with pseudoachalasia, but endoscopic biopsy diagnosed cancer in only two of them. CT scans gave no clear evidence of malignancy in any patient, although three scans had nonspecific findings that, in retrospect, probably indicated malignancy. There were no distinguishing manometric findings. When pseudoachalasia is suspected on the basis of a constellation of findings, such as advanced age, rapid weight loss, and difficulty in passing the endoscope through the gastroesophageal junction of a nondilated esophagus, negative findings on biopsy and CT scans should not lead to a false reassurance of a benign disorder, and repeated biopsy and scans or surgical exploration may lead to the diagnosis of pseudoachalasia.


The synthesis and evaluation of macrocyclic gadolinium-DTPA-bis(amide) complexes as magnetic resonance imaging contrast agents.
The authors found that DTPA bis(amide) macrocycles can be prepared in reasonable yields using simple methods and readily available starting materials. Gadolinium complexation is facile and gives rise to monomeric and dimeric species. The "pocket size" influences the solid state structure of the final complex, with Gd-DTPA-EAM existing as a dimer wherein the macrocycle bridges between two metal centers. Increasing the size of the bridging diamide moiety yields a macrocycle with a sufficiently large pocket to allow for the formation of nine-coordinant monomeric complexes. The solution behavior of all the complexes studied is consistent with the complex being present as monomers. All complexes display kinetic lability comparable to Gd-DTPA-BMA. The measured KTherm and KSel values of the complexes vary with the size of the pocket. Values similar to those observed for Gd-DTPA-BMA have been obtained with Gd-DTPA-OAM. There appears to be a good correlation between log K(Gd/Zn) and the acute toxicity for the complexes studied, with Gd-DTPA-OAM showing a toxicity value similar to that of Gd-DTPA-BMA. Although many of these complexes are chemically interesting, they do not offer any unique advantages as new magnetic resonance imaging contrast agents compared with the DOTA- and DTPA-based products currently used clinically.


Template-free synthesis of Ta3N5 nanorod arrays for efficient photoelectrochemical water splitting.
We report the template-free synthesis of Ta3N5 nanorod array films grown on Ta foil by a combination of a vapor-phase hydrothermal process and subsequent nitriding. The Ta3N5 nanorod array film modified with Co(OH)x when used as a photoanode in a photoelectrochemical cell for water splitting yields a stable photocurrent density of 2.8 mA cm(-2) at 1.23 VRHE under AM 1.5G simulated sunlight. The incident photon-to-current conversion efficiency at 480 nm is determined to be 37.8%.


Evaluation of Hsp47 expression in heat-stressed rat myocardial cells in vitro and in vivo.
The aim of the present study was to identify the correlation between expression of heat shock protein 47 (Hsp47) and stress injury in heat-stressed myocardial cells and to compare variations in Hsp47 expression in rat myocardial cells exposed to different heat stress for varying periods in vitro and in vivo. Exposure to heat stress at 42°C resulted in similar induction patterns of the heart damage-related enzyme aspartate aminotransferase in the supernatants of H9c2 cells and in the serum of rats. Histological analysis revealed that both H9c2 cells and heart tissues displayed cellular degeneration in response to different periods of heat stress. Hsp47 was constitutively expressed in the cytoplasm of H9c2 cells at all time points during heat stress, which was consistent with observations in heart fibers in vivo. Immunoblotting analysis revealed no significant difference between the expression of Hsp47 in H9c2 cells and heart tissue. However, the expression of hsp47 mRNA in response to heat stress was significantly increased in H9c2 cells at 60 min (P < 0.01) and 100 min (P < 0.01), which was comparable to that at 100 min (P < 0.01) in the rat heart. Thus, Hsp47 was elevated significantly after hyperthermia at the mRNA level but not at the protein level both in vitro and in vivo. The results suggest that Hsp47 turnover may increase during heat stress or that Hsp47 consumption exceeds its production.


Effects of novel brominated flame retardant TBBPA on human airway epithelial cell (A549) in vitro and proteome profiling.
The cellular toxicity response of human airway epithelial cells (A549) to tetrabromobisphenol (TBBPA) was assessed in vitro. Cell viability, levels of intracellular reactive oxygen species (ROS), lipid peroxidation (MDA), and caspase-3 activity were determined after A549 treated with varying concentrations of TBBPA. A comparative proteomic analysis was performed in cells treated with different concentrations of TBBPA (0, 10, and 40 μg/mL). Two-way anova analysis showed that cell viability was significantly decreased after treatment by TBBPA with a concentration of 16 μg/mL for 48 hr, however, the caspase-3 activities, ROS generation, and MDA content increased. Ultrastructural observation revealed that the cell was morphological damaged after exposure to 64 μg/mL TBBPA, with mitochondria seriously injured and the smooth endoplasmic reticulum dilated. There was a good correlation between ROS generation and mitochondrial dysfunction. Seventeen differentially expressed proteins involved in various biological processes were identified. These findings provide a basis for understanding the mechanisms of cell dysfunction and perturbation of antioxidant status induced by additive flame retardant on airway epithelial cells.


A radiation exposure meter for technologists.
The need for Quality Assurance Programs has made it necessary for the technologist to have an accurate yet simple to use instrument for measuring radiation exposure. A unique commercial instrument is described that can help the technologist determine radiation output, half value layer, mAs reciprocity, and fluoroscopy exposure rates. The ability of the technologist to make these measurements will lead to reduction of repeat films and radiation exposure to the patient.


Left atrial strain analysis in the realm of pediatric cardiology: Advantages and implications.
Left atrial (LA) strain analysis has emerged as a noninvasive technique for assessing LA function and early detection of myocardial deformation. Recently, its application has also shown promise in the pediatric population, spanning diverse cardiac conditions that demand accurate and sensitive diagnostic measures. This research endeavors to explore the role of LA strain parameters and contribute to the growing body of knowledge in pediatric cardiology, paving the way for more effective and tailored approaches to patient care. A comprehensive literature review was conducted to gather evidence from studies using echocardiographic strain imaging techniques across pediatric populations. LA strain parameters exhibited greater sensitivity than conventional atrial function indicators, with early detection of diastolic dysfunction and LA remodeling in pediatric cardiomyopathy, children with multisystem inflammatory syndrome, rheumatic heart disease, as well as childhood renal insufficiency and obesity offering prognostic relevance as potential markers in these pediatric subpopulations. However, there remains a paucity of evidence concerning pediatric mitral valve pathology, justifying further exploration. LA strain analysis carries crucial clinical and prognostic implications in pediatric cardiac conditions, with reliable accuracy and sensitivity to early functional changes.


User Authorization at the Molecular Scale.
Electronic user authorization systems help us maintain our privacy in many aspects of everyday life. However, the increasing difficulty to secure access and/or information digitally has inspired chemists to devise alternative, molecular approaches, in which users are identified by chemical means. The potential advantages of using molecular user authentication systems over conventional electronic devices are their versatility and unusual operating principles, which complicate replicating and, consequently, breaking into molecular security devices. Their molecular scale is another unique property that enables hiding such systems and, consequently, applying steganography as an additional layer of protection. Although the area of molecular-based user authorization is still in its infancy, the development of various molecular keypad locks and, more recently, a password-protected molecular cryptographic machine, indicate the possibility of protecting information at the molecular scale.


Comparison of a dipstick dot-ELISA with commercial assays for anti-dengue virus IgM antibodies.
Dengue virus infections have undergone dramatic expansion in range, affecting several tropical and subtropical regions of the world. Dengue virus causes life-threatening complications characterized by dengue hemorrhagic fever and dengue shock syndrome. No standard validated test systems are available for serological diagnosis of dengue virus infection. This creates problems in the diagnosis and proper management of patients. Evaluation of a Defense Research and Development Establishment (DRDE) dengue virus dipstick dot-ELISA test, developed in house, vis-à-vis commercially available immunodiagnostic kits was carried out for detection of IgM antibodies. The DRDE dengue dipstick dot-ELISA was performed on the basis of the dot-ELISA principle. Commercial tests, namely, the Panbio Dengue IgM Capture ELISA system (Panbio, Sinnamon Park, Australia) and Pathozyme Dengue M (Omega Diagnostics, Alva, UK), were performed according to the manufacturers' protocols. Ninety-one serum samples collected from the states of Kerala and Delhi, India during August and November of 2004 were used in the present study. The overall agreement among all three tests was found to be only 72.16% for IgM antibodies. Correlations between the DRDE dipstick dot-ELISA and the Panbio kit, between the DRDE dipstick dot-ELISA and the Pathozyme Dengue M kit, and between the Panbio kit and the Pathozyme Dengue M kit were found to be 96, 93, and 94%, respectively. Although the Panbio kit is widely used in various laboratories in India, the DRDE dipstick dot-ELISA promises to be a useful kit because of its field applicability and comparable sensitivity.


A review of academic tenure in radiologic technology.
The concept of academic tenure is reviewed, with special interest to the radiologic technology educator. Both the community college and university tenure systems are discussed. Recommendations for further research and future policy are also presented.


Effect of 24-week treatment with telmisartan on myocardial structure and function: relationship to insertion/deletion polymorphism of the angiotensin-converting enzyme gene.
The aim of the present study was to assess the effect of treatment with the angiotensin II receptor blocker telmisartan for 24 weeks on myocardial structure and function in patients with essential hypertension, and the relationship between this effect and the structural polymorphism of the angiotensin-converting enzyme (ACE) gene. Thirty-five patients with essential hypertension and left ventricular hypertrophy (LVH) without other associated morbidity were included in an open-label, non-comparative study. The patients were treated with telmisartan 40-80 mg once daily. In the final analysis, there were 29 patients who received the full course of treatment and were evaluated echocardiographically before and after treatment by the same blinded investigator, and myocardial structure and function were analysed. The myocardial mass of the left ventricle was determined in M-mode. Assessment of diastolic function of transmitral blood flow was performed using pulsed Doppler echocardiography. All patients were genotyped for insertion/deletion (I/D) polymorphism of the ACE gene. Telmisartan produced a significant reduction in left ventricular mass index from 140.4 +/- 48.6 to 128.7 +/- 40.6 g/m2 that was accompanied by an improvement in characteristics of diastolic function. The decrease in LVH was more significant in the ID genotype group than in the II and DD groups. Thus, prolonged treatment with telmisartan is accompanied by an improvement in myocardial structure, expressed as a reduction in left ventricular mass and function that is more marked in patients with ID genotype of the ACE gene.


Body Mass Index and Related Risk Factor of Sinusitis Among Adults in Saudi Arabia: A Cross-Sectional Study.
Chronic rhinosinusitis (CRS) is a widespread condition worldwide that is leading to a significant burden on society in terms of healthcare consumption and productivity loss. Multiple risk factors have been implicated in the pathogenesis of CRS, such as nasal allergies, bronchial asthma, smoking, nasal polyps, and immune system-related diseases. The present study aimed to assess the prevalence of CRS, the most common risk factors, and the association between diabetes, body mass index (BMI), and CRS in Saudi Arabia. A cross-sectional study was conducted through random sampling that included 3602 participants from different regions of Saudi Arabia from November 2022 to January 2023. Electronic questionnaires were used for data collection. A total of 3602 individuals responded to our questionnaires; 948 (26.3%) were diagnosed by physicians as having chronic rhinosinusitis, and 75.1% were females. The majority (41.5%) were between the ages of 18 and 28 years. We found that smoking was significantly associated with sinusitis (OR 2.01, 95% CI 1.23-5.69) (p value 0.003) and that obesity was also significantly associated with sinusitis, 17.0% of persons with sinusitis were obese class I (BMI 30-35 kg/m2); 7.8% were obese class II (BMI>35 kg/m2); and 29.4% were overweight, whereas 45.8% were of normal weight. All percentages differ significantly from persons with normal weight (p value = 0.000). The most common risk factors for sinusitis were nasal allergies (44.4%), stuffy nose (22.8%), and deviation of the nasal septum (19.2%). All percentages differ significantly from persons without comorbidity (p value = 0.000). The present study showed a slight increase in the prevalence of CRS in Saudi Arabia, which is attributable to increased exposure to allergens. The most common risk factors were nasal allergies, nasal blockage, deviation of the nasal septum, and asthma. There was a significant correlation between CRS and BMI in the form of increased prevalence in overweight and obese compared to normal-weight individuals.


Enzymatic solubilization of membrane immunoglobulin (M-Ig) from rabbit lymphocytes with phospholipase A2 (PL-A2) and phospholipase C (PL-C).
Enzymatic solubilization of M-Ig from rabbit lymph node cells was investigated using highly purified PL-A2 and PL-C. The combined treatment with PL-A2 (50 I.U./ml) and PL-C (20 I.U./ml) caused optimal solubilization of the membrane components from the 125I-labeled lymphocytes, but the treatment with either enzyme alone did not. The solubilized M-Ig was isolated and characterized as the membrane component which was specifically co-precipitable with homologous antigen-antibody complex. The solubilized M-Ig associated with some other membrane constituents was eluted in a void volume fraction by gelfiltration on a column of Sepharose 6B, and recovered at the interface between 30 and 40% sucrose layers by the density gradient centrifugation. The isolated component could be further separated by SDS-polyacrylamido gel electrophoresis into four radioactive polypeptides with apparent mol wt of 7 approximately 8 X 10(4), 4 approximately 5 X 10(4), 3 approximately 3.5 X 10(4) and 2 approximately 2.5 X 10(4), respectively. The results suggest that the enzymatic solubilization of lymphocyte M-Ig is a useful procedure to investigate further characteristics of M-Ig and their biological function related to the intracellular mechanisms of immune response.


Assessing Medical Students' Attitudes and Knowledge Regarding LGBTQ Health Needs Across the United States.
The lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) community experiences health disparities. It is thus imperative that medical trainees receive training in the care of LGBTQ community. The objective of this study was to identify gaps in knowledge and comfort among medical school students in providing care for the LGBTQ community. An online survey was administered to medical students at 3 institutions in the United States from December 2020 to March 2021. Using a Likert scale, the survey assessed attitudes, comfort, and knowledge in providing care for the LGBTQ community. The survey included questions for each specific LGBTQ population. Results were quantified using descriptive and stratified analyses, and an exploratory factor analysis was used to calculate attitude summary measure (ASM) scores. A total knowledge score was calculated, with higher values indicating greater knowledge. Among the 300 medical students who completed the survey, the majority were female (55.7%), White (54.7%), and heterosexual (64.3%). The majority of medical students felt comfortable (strongly agree/agree) participating in the care of lesbian (94.3%), gay (96.0%), and bisexual (96.3%) patients; this percentage dropped to 82.3% for non-binary and 71.3% for transgender patients. Only 27.0% of medical students reported confidence in their knowledge of health needs of transgender patients. LGBTQ self-identification, percent of core rotations completed in school, region of country, and friends and/or family who are part of the LGBTQ community were significantly associated with various ASM scores. Knowledge questions yielded high percentages of "neutral" responses, and medical students who identified as LGBTQ had significantly higher total knowledge scores. Overall, the surveyed medical students feel comfortable and willing to provide care for LGBTQ persons. But, there is limited knowledge about specific LGBTQ health needs. More education and training in the needs of transgender and non-binary patients, in particular, is indicated.


Amikacin Liposomal Inhalation Suspension in the Treatment of Mycobacterium abscessus Lung Infection: A French Observational Experience.
Mycobacterium abscessus infections remain difficult to manage in both cystic fibrosis (CF) and non-CF patients and reported clinical outcomes are largely unsatisfactory. Clinical trial data are limited and no approved therapies are currently available for the management of M abscessus lung diseases. As an alternative, cohort studies may provide insightful information into the management of M abscessus pulmonary disease. Based on a retrospective observational cohort study, we investigated the safety and efficacy of amikacin liposome inhaled suspension (ALIS) as an adjunct to a standard antibiotic regimen for M abscessus lung infection in both CF and non-CF patients. We also assessed the association of patient drug compliance with culture conversion and clinical outcomes. Twenty-six patients had long-term follow-up data available. Culture conversion was achieved in 54% (14/26) of the patients with no difference between CF and non-CF patients after an average treatment duration of 10 months. Patient treatment compliance was significantly better in the converter group compared to nonconverters with an odds ratio of 44.78 associated with good compared to poor patient compliance. Overall, 9 patients (35%) experienced an adverse event that led to treatment discontinuation. ALIS appears beneficial in both CF and non-CF populations with M abscessus lung disease.