Interactions between auditory and somatosensory feedback for voice F0 control.
Previous studies have demonstrated the importance of both kinesthetic and auditory feedback for control of voice fundamental frequency (F0). In the present study, a possible interaction between auditory feedback and kinesthetic feedback for control of voice F0 was tested by administering local anesthetic to the vocal folds in the presence of perturbations in voice pitch feedback. Responses to pitch-shifted voice feedback were larger when the vocal fold mucosa was anesthetized than during normal kinesthesia. A mathematical model incorporating a linear combination of kinesthesia and pitch feedback simulated the main aspects of our experimental results. This model indicates that a feasible explanation for the increase in response magnitude with vocal fold anesthesia is that the vocal motor system uses both pitch and kinesthesia to stabilize voice F0 shortly after a perturbation of voice pitch feedback has been perceived.


Omnichannel in the fashion industry: A qualitative analysis from a supply-side perspective.
Currently, many companies are abandoning multichannel and turning to a much more centralized model known as omnichannel, in order to gain a competitive advantage by integrating and optimizing different channels and thus the client has a unique experience. Within this context, the aim of this study is to analyse the omnichannel digital marketing strategies implemented by Spanish fashion and accessories companies in order to provide pleasant shopping experiences to their online consumers. To that end, a qualitative analysis has been carried out, specifically consisting of in-depth interviews conducted with marketing managers who implement digital strategies in their businesses to improve the online experience of consumers in an omnichannel context. From a practical perspective, this study can help inform companies' decision-making on how to best develop their consumers' omnichannel experience and, in consequence, improve consumers' behavioural responses such as personal participation, satisfaction and engagement with the firm.


[Comparative human studies of a new anti-hypertensive drug (2,6-dichloro-benzylidene-aminoguanidine acetate) and methyldopa in hypertensive patients].
A between-patients trial between a new anti-hypertensive drug (Guanabenz) and methyldopa in subjects with essential hypertension showed the new preparation to be active and endowed with a satisfactory therapeutic index.


Severe monkeypox with superimposed bacterial infection in an immunocompetent patient: A case report.
Monkeypox, a member of the Orthopoxvirus genu, has been the center of global attention since it has been declared a public health emergency by the World Health Organization. Typically, it is a self-limiting disease; however, it can occasionally have severe presentations in patients with underlying conditions, such as HIV, malignancy, and transplantation. In this article, we will present a case of an immunocompetent patient with a severe presentation of monkeypox. The patient presented with facial pustules with superimposed bacterial infection; furthermore, he had painful vesicles in oral and nasal mucosa and the penis. Dermatologic conditions such as atopic dermatitis has been associated with severe monkeypox. While our patient does not have a history of atopic dermatitis, he does report contact dermatitis as well as a history of skin infections. Researchers have hypothesized that disruption of the skin barrier allows for proliferation of the monkeypox virus; therefore, it is important to take a thorough history of the patient's skin conditions. Lastly, we described the use of Tecovirimat in our patient. Although it is impossible to demonstrate the efficacy of this medication without a randomized clinical trial, our patient seemed to have a faster improvement of the lesions after initiating this antiviral.


Potentiation of the tumor cytotoxicity of melphalan by vasodilating drugs.
Previous studies have shown that several vasoactive drugs can selectively reduce blood flow and increase hypoxia in experimental tumor systems. Our studies with one such agent, the vasodilator hydralazine, have clearly demonstrated that it can increase the tumor cytotoxicity of drugs which are known to be more toxic under hypoxic conditions. We have now extended our investigations to determine whether such selective reductions in tumor blood flow induced by hydralazine can increase the tumor cytotoxicity of other classes of cancer chemotherapeutic drugs. Our initial studies have involved the alkylating agent melphalan. Administration of hydralazine (5 mg/kg IP) at various times before or after melphalan results in increased tumor cytotoxicity in the Lewis lung carcinoma. An enhancement factor of between 2 and 3 was obtained in this tumor system. Similar results are observed if the vasodilator cadralazine is used. In contrast to the enhancement of the tumor cytotoxicity of melphalan by hydralazine, systemic toxicity is only increased by a factor of 1.2. Therefore, therapeutic gain may accrue from the use of vasodilating agents in combination with melphalan. Studies using spheroids to establish the mechanism responsible for the enhanced tumor cytotoxicity indicate that both hypoxia and pH can influence melphalan toxicity.


Circular dichroism and its application to the study of biomolecules.
Circular dichroism (CD) is an excellent method for the study of the conformations adopted by proteins and nucleic acids in solution. Although not able to provide the beautifully detailed residue-specific information available from nuclearmagnetic resonance (NMR) and X-ray crystallography, CD measurements have two major advantages: they can be made on small amounts of material in physiological buffers and they provide one of the best methods for monitoring any structural alterations that might result from changes in environmental conditions, such as pH, temperature, and ionic strength. This chapter describes the important basic steps involved in obtaining reliable CD spectra: careful instrument and sample preparation, the selection of appropriate parameters for data collection, and methods for subsequent data processing. The principal features of protein and nucleic acid CD spectra are then described, and the main applications of CD are discussed. These include: methods for analyzing CD data to estimate the secondary structure composition of proteins, methods for following the unfolding of proteins as a function of temperature or added chemical denaturants, the study of the effects of mutations on protein structure and stability, and methods for studying macromolecule-ligand and macromolecule-macromolecule interactions.


The beta1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2beta protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition.
BALB/c mice immunized with recombinant Trypanosoma cruzi ribosomal P2beta protein (TcP2beta) develop a strong and specific antibody response against its 13 residue-long C-terminal epitope (peptide R13: EEEDDDMGFGLFD) that has a concomitant beta1-adrenergic stimulating activity. However, other animals that undergo similar immunizations seem tolerant to this epitope. To evaluate further the antibody response against the ribosomal P proteins, 25 BALB/c and 25 Swiss mice were immunized with TcP2beta. From the 50 animals, 31 developed a positive anti-R13 response, whereas 19 were non-responsive. From the 31 anti-R13 positive mice, 25 had anti-R13 antibodies that recognized the discontinuous motif ExDDxGF, and their presence correlated with the recording of supraventricular tachycardia. The other six had anti-R13 antibodies but with a normal electrocardiographic recording. These anti-R13 antibodies recognized the motif DDxGF shared by mammals and T. cruzi and proved to be a true anti-P autoantibody because they were similar to those elicited in Swiss, but not in BALB/c mice, by immunization with the C-terminal portion of the mouse ribosomal P protein. Our results show that the recognition of the glutamic acid in position 3 of peptide R13 defines the ability of anti-R13 antibodies to react with the motif AESDE of the second extracellular loop of the beta1-adrenergic receptor, setting the molecular basis for their pathogenic beta1 adrenoceptor stimulating activity.


Sensitive measurement of fragmented red cell population using flow cytometry, and its application for estimating thrombotic microangiopathy after stem cell transplantation.
Thrombotic microangiopathy (TMA) is one of the lethal complications after hematopoietic stem cell transplantation (SCT). The levels of fragmented red cells (FRCs), thrombomodulin (TM), and factor VIII-related antigen in the blood are the most important markers for estimating TMA. However, the FRC level has been measured by using microscopy and the naked eye; therefore, an improvement in technology to objectively count FRC is necessary. We established a novel technique to sensitively measure FRC as glycophorin A dull-positive small particles using a flow cytometer and estimated its reliability in patients treated with SCT. The blood level of FRC was compared with other clinical data in 257 blood samples in 16 clinical courses after SCT of 15 patients. Sorted glycophorin A dull-positive small particles morphologically showed FRC. Measured FRC percentage had a weak correlation with serum levels of lactate dehydrogenase (LDH) and total bilirubin but not with TM level, whereas TM showed a weak correlation with the levels of aspartate aminotransferase and LDH. In a patient with fulminant TMA, decrement of the FRC level led to improvement in liver parameters after treatment, presumably due to the rapid clearance of FRC, and increased simultaneously with the levels of LDH and bilirubin by the TMA recurrence. Levels of FRC percentage and TM were independent parameters of TMA. This novel technique may be used as a standard methodology in diagnosing TMA.


Contaminated Perry in Patagonia Argentina: A Case Study.
Perry is a beverage obtained by fermentation of pear juice, popular in the North Hemisphere. In Argentina it is an emerging market, particularly in the Patagonian region. The aim of this work is to describe and to evaluate the spoilage yeasts associated to six perry samples showing signs of microbiological contamination from a local craft perry company in North Patagonian region. Eighteen yeasts were isolated from four of the six perry samples where Brettanomyces custersianus, Brettanomyces bruxellensis and Zygosaccharomyces parabailii were identified. The growth capacity of these isolates in the presence of antimicrobial agents (sulfite and potassium sorbate) was analyzed in solid media. Growth parameters in sterile perry must was evaluated and the production of undesirable compounds were evaluated, products were characterized in terms of their aromatic and physicochemical features. The yeasts Z. parabailii NPCC1791 was able to grow on plates containing sulfite concentrations of up to 4 mM and produced high methanol concentrations in perry. Additionally, B. bruxellensis NPPC1792 was able to produce methanol as well as high concentrations of volatile phenols including 4-ethylphenol and 4-ethylguaiacol. These results demonstrate the potential of these species as perry contaminants. Given the lack of studies describing the contaminating yeasts in perry production, this work represents the first report about perry spoilage yeasts in Argentina, with this knowledge, control strategies can be developed to prevent microbiological contamination and minimize product loss.


Second meiotic nondisjunction is not increased in postovulatory aged murine oocytes fertilized in vitro.
We used an in vitro fertilization system to examine the effects of postovulatory oocyte age on nondisjunction at the second meiotic division. After ovulatory-inducing injections of hormone, we recovered mouse oocytes either at the estimated time of ovulation (controls) or 2, 4, 5, 10, or 14 h later. Oocytes were subjected to an in vitro fertilization procedure, and chromosomal preparations were made from first cleavage metaphase eggs. The first cleavage assay reveals morphologically distinguishable paternal and maternal chromosomes. Many of the aged oocytes were activated rather than fertilized by the in vitro procedure, but could still be analyzed for nondisjunction. We found a tendency toward retention of the second polar body after 10 and 14 h aging. A total of 488 maternal genomes, 290 of which were in the control group, were analyzable for nondisjunction. Seven hyperhaploid genomes (2.4%) were observed in the controls and 6 (3.0%) in the combined aged group. The difference between these two frequencies is not significant (Gadj = 0.164, P greater than 0.50). In the aged group, one hyperhaploid genome was in the 2-h population, three in the 5-h population, and two in the 10-h population. We were unable to find any significant increase in the frequency of nondisjunction after postovulatory oocyte aging.


Cognitive function following acute sleep restriction in children ages 10-14.
Various aspects of human performance were assessed in children after sleep loss. Sixteen children (7 males, 9 females) between the ages of 10 and 14 years. Children were randomly assigned to either a control (CTRL) group, with 11 hours in bed, or an experimental sleep restriction (SR) group, with 5 hours in bed, on a single night in the sleep laboratory. Both groups were evaluated the following day with a battery of performance and sleepiness measures. Psychomotor and cognitive performance tests were given during four 1-hour testing sessions at 2-hour intervals. A multiple sleep latency test (MSLT) documented shorter latencies for SR children than controls. Significant treatment differences were discovered in three of four variables of verbal creativity, including fluency, flexibility, and average indices. There were also group differences found on the Wisconsin Card Sorting Test (WCST), which may be indicative of difficulty learning new abstract concepts. Measures of rote performance and less-complex cognitive functions, including measures of memory and learning and figural creativity, did not show differences between groups, perhaps because motivation could overcome sleepiness-related impairment for these tasks. Higher cognitive functions in children, such as verbal creativity and abstract thinking, are impaired after a single night of restricted sleep, even when routine performance is relatively maintained.


Combining the dual antibacterial and regenerative activities of platelet-rich plasma with β-lactams to mitigate MRSA-infected skin wounds.
The emergence of multidrug-resistant bacteria contributes to the necessity of developing novel infection treatment approaches. This study was designed to evaluate the antimicrobial and wound healing activities of platelet-rich plasma (PRP) in combination with β-lactams (ampicillin and/or oxacillin) for the application on methicillin-resistant Staphylococcus aureus (MRSA)-infected skin. PRP was collected from the peripheral blood of healthy donors. The anti-MRSA activity was tested through a growth inhibition curve, colony-forming unit (CFU), and SYTO 9 assay. The PRP incorporation lowered the minimum inhibitory concentration (MIC) of ampicillin and oxacillin against MRSA. The combination of β-lactams together with PRP showed a three-log CFU reduction of MRSA. The major components of PRP for eliminating MRSA were found to be the complement system and iron sequestration proteins, according to the proteomic analysis. The adhesive bacterial colony in the microplate was decreased from 2.9 × 107 to 7.3 × 105 CFU after the treatment of cocktails containing β-lactams and PRP. The cell-based study indicated that keratinocyte proliferation was stimulated by PRP. The in vitro scratch and transwell experiments revealed that PRP improved keratinocyte migration. In the MRSA-infected mouse skin model, PRP appeared to show a synergistic effect for wound area reduction by 39% when combined with β-lactams. The MRSA burden in the infected area was lessened two-fold after topical administration of the combined β-lactams and PRP. PRP inhibited macrophage infiltration in the wound site to shorten the inflammatory phase and accelerate the initiation of the proliferative phase. No skin irritation was detected with the topical delivery of this combination. Our findings suggested that β-lactams plus PRP was applicable to alleviate the problems associated with MRSA via dual antibacterial and regenerative activities.


Effects of garlic on the induction of ventricular fibrillation.
Previous studies have shown that oral and intravenous administrations of garlic provide a significant antiarrhythmic effect and improve defibrillation efficacy. We tested the hypothesis that garlic could decrease the inducibility of ventricular arrhythmia. Twenty-one pigs (25-30 kg) were divided into three groups. In each group, the ventricular fibrillation threshold (VFT) and the upper limit of vulnerability (ULV) were determined. After the control VFT and ULV values were obtained, solutions containing 20 mg/kg (group 1, n = 7) and 40 mg/kg (group 2, n = 7) of garlic (1.3% allicin) were administered intravenously. The VFT and ULV were determined again at the end of garlic infusion. In group 3 (n = 7), 100 mL of normal saline was administered instead of garlic. The VFT values in groups 1 and 2 were not different from the control VFT. The ULV in group 1 was not different from the control ULV. However, the ULV in group 2 (328 +/- 58 V, 8 +/- 3 J) was significantly lower than the control ULV (415 +/- 24 V, 13 +/- 2 J), thus accounting for the reduction of approximately 21% by peak voltage and approximately 38% by energy. The effective refractory period and diastolic pacing threshold were not altered after garlic infusion. Saline did not alter VFT or ULV. Garlic cannot alter the VFT, but it significantly decreases the ULV in a dose-dependent pattern, indicating that it can reduce the range of the stimulation strength between the VFT and ULV (vulnerability window) during the vulnerable period of a cardiac cycle.


Syntheses of metabolites of S-carboxymethyl-L-cysteine and S-methyl-L-cysteine and of some isotopically labelled (2H, 13C) analogues.
The chemical syntheses of human metabolites of S-carboxymethyl-L-cysteine (3) and S-methyl-L-cysteine (12) are described. The additional preparation of some 2H- and 13C-labelled isotopomers enabled the direct evaluation of the stabilities of 3 and 12 under physiological conditions and also facilitated the unambiguous assignments of the signals in the 13C-NMR spectra of all compounds mentioned.


Frontline Science: Cytokine-mediated developmental phenotype of mouse eosinophils: IL-5-associated expression of the Ly6G/Gr1 surface Ag.
Eosinophils have broad and extensive immunomodulatory capacity; recent studies have focused on the roles of distinct eosinophil subsets in specific tissue microenvironments. Ly6G is a GPI-linked leukocyte surface Ag understood primarily as a marker of mouse neutrophils, although its full function is not known. Here, we show that Ly6G/Gr1, detected by mAbs 1A8 (anti-Ly6G) and RB6-8C5 (anti-Gr1), is detected prominently on a significant fraction of eosinophils from mouse bone marrow and bone marrow-derived culture, with fractions expressing this Ag increasing in IL-5-enriched microenvironments. Among our findings, we identified SiglecF+ Gr1+ eosinophils in bone marrow from naïve, allergen-challenged and IL-5 transgenic mice; SiglecF+ Gr1+ eosinophils were also prominent ex vivo in bone marrow-derived eosinophils (bmEos) in IL-5-enriched culture. Reducing the IL-5 concentration 20-fold had no impact on the rate of generation of SiglecF+ bmEos but did result in a marked increase in the Gr1- fraction (from 17.4 ± 2% to 30 ± 2.3%, ***P < 0.005). Reducing the IL-5 concentration also enhanced chemotaxis; SiglecF+ Gr1- bmEos were considerably more responsive to eotaxin-1 than were their SiglecF+ Gr1+ counterparts. These results suggest that (i) IL-5 regulates the expression of Ly6G/Gr1, either directly or indirectly, in cells of the eosinophil lineage, (ii) eosinophils generated in response to high concentrations of IL-5 can be distinguished from those generated under homeostatic conditions by expression of the Ly6G/Gr1 cell surface Ag, and (iii) expression of Ly6G/Gr1 may have an impact on function, directly or indirectly, including the potential to undergo chemotaxis in response to eotaxin-1.


Biomechanics and biology of external fixation of distal radius fractures.
External fixation is a versatile and useful tool for management of complex fractures. There is little to choose between the various types of commercially available fixators, and it is important to use one that allows the surgeon adequate versatility and follows sound biomechanical principles. Ligamentotaxis can be used effectively to reduce the most difficult fractures; however, over-distraction and prolonged traction are harmful and should be avoided. Certain types of fractures do not respond to treatment with ligamentotaxis alone and require adjunctive treatment, such as limited internal fixation. A single K-wire significantly adds to the stability of fixation and should be considered in all cases. Understanding the basic mechanical principles and respect for pin-bone biology allow for successful use of external fixation with minimal complications.


The painful eye: external and anterior segment causes.
When a patient presents to a medical practitioner with a painful eye, the initial history is extremely valuable in determining the cause of the complaint. The patient should be questioned specifically about the onset and duration of symptoms; description of the pain; exacerbating and mitigating factors; associated pruritus, discharge, or photophobia; and any previous occurrences. It is important to inquire about the patient's past medical history, past ocular history (including surgeries, trauma, contact lens wear, and family history of glaucoma), systemic and ocular medications, and allergies. A careful examination of the patient's skin, face, eyelids, conjunctiva, sclera, cornea, and anterior chamber should be performed. In this article, the authors describe a variety of external diseases and anterior segment causes of a painful eye, many of which can be diagnosed from the initial history. The article works systematically, beginning externally with the eyelids and conjunctiva and progressing internally toward the cornea and anterior chamber.


Genetic evidence of interspecies introgression of mitochondrial genomes between Trichinella spiralis and Trichinella britovi under natural conditions.
Trichinellosis is a zoonotic disease caused by Trichinella muscle larvae (ML) through ingestion of raw or undercooked meat. To date, 12 taxa are recognized in this genus, of which four are circulating in Europe (Trichinella spiralis, Trichinella nativa, Trichinella britovi and Trichinella pseudospiralis). T. spiralis and T. britovi circulate in European wildlife and occur simultaneously in the same host species. The possibility of hybrid formation between T. britovi and T. spiralis has hardly been addressed and so far, results of experimental hybridisation attempts between T. britovi and T. spiralis are inconclusive. The aim of the present study was to analyse molecular polymorphisms of single T. spiralis and T. britovi ML from natural infections based on nuclear 5S rDNA intergenic spacer region (5S rDNA-ISR) and mitochondrial cytochrome c oxidase 1 (CO1) gene sequences. Six haplotypes of the 5S rDNA intergenic spacer region (5S rDNA-ISR) and 14 of the cytochrome c oxidase 1 (CO1) gene were demonstrated in 89 individual T. britovi ML from Latvia and Poland. In contrast, only two haplotypes were observed at both 5S rDNA-ISR and CO1 of 57 individual T. spiralis ML from Polish wild boar and red foxes. Moreover, this study demonstrates hybridisation in eight individual ML between T. britovi and T. spiralis under natural conditions in four Polish wild boar and two red foxes, revealed by combining 5S rDNA-ISR and CO1 sequence information of individual Trichinella ML. To our knowledge, this is the first report of interspecies hybridisation between T. spiralis and T. britovi under field conditions.


Diltiazem, verapamil, and quinidine in patients with chronic atrial fibrillation.
The comparative effects of diltiazem and verapamil in 30 patients with long-standing atrial fibrillation were evaluated in a prospective clinical trial. After a one- to two-day washout period during which drugs other than digoxin were withdrawn, patients were randomly assigned to diltiazem or verapamil treatment groups. All therapy was double blind. Both drugs were given in ascending doses as follows: days 1-6 (part I): diltiazem, 180 mg/d, or verapamil, 240 mg/d; days 7-12 (part II): diltiazem, 360 mg/d, or verapamil, 480 mg/d. Patients failing to convert to sinus rhythm after 12 days had dosage reduced to 180 mg/d of diltiazem or 240 mg/d of verapamil, and quinidine, 750 mg/d, was coadministered for another six days (part III). Medication compliance was verified by frequent measurement of serum drug concentrations. Three verapamil patients dropped out during part I due to adverse reactions (dyspnea, pulmonary congestion, skin rash, or hepatotoxicity). The higher dosage of either verapamil or diltiazem in part II was not well tolerated, and in eight patients part III had to be initiated early due to symptomatic bradycardia. Only one patient in the diltiazem group converted to sinus rhythm, whereas five converted with verapamil (two with verapamil alone, three when combined with quinidine). Thus, diltiazem and verapamil alone are unlikely to convert atrial fibrillation to sinus rhythm. The combination of verapamil and quinidine, however, is a potentially useful pharmacologic approach, having converted atrial fibrillation to sinus rhythm in nearly 50% of patients.


Bipolar I and II disorders in a random and representative Australian population.
To assess the prevalence of bipolar I and II disorders in an Australian population. The Mood Disorder Questionnaire (MDQ) was administered to 3015 respondents in a random and representative sample in South Australia. Health status, quality of life and demographic data were also collected. There was a 2.5% lifetime prevalence of bipolar I and II disorders delineated by the MDQ. Those people had a significantly greater use of services and a poorer health status and quality of life than those who were MDQ-negative. These results in an Australian population are consistent with other international studies showing a greater prevalence of bipolar disorders than hitherto appreciated.


Changes in choroidal vascular parameters following pan-retinal photocoagulation using swept-source optical coherence tomography.
To assess the effect of pan-retinal photocoagulation (PRP) on choroidal vascular parameters in eyes with advanced diabetic retinopathy (DR). Forty patients (65 eyes) with severe nonproliferative DR or proliferative DR who underwent PRP were included. Changes in choroidal vascular parameters were assessed at 3, 6, and 12 months after PRP by using swept-source optical coherence tomography (OCT) and OCT angiography and were compared with baseline values. Choroidal vascularity index (CVI) significantly decreased from 66.27% ± 1.55% at baseline to 65.85% ± 1.61%, 65.77% ± 1.29%, and 65.74% ± 1.60% at 3, 6, and 12 months after PRP, respectively. The ratio of luminal area to stromal area (L/S ratio) also significantly decreased from 1.98 ± 0.15 at baseline to 1.94 ± 0.14, 1.95 ± 0.13, and 1.93 ± 0.14 at 3, 6, and 12 months after PRP, respectively. The subfoveal choroidal thickness (SFCT) similarly showed a significant decrease from 319.50 ± 56.64 μm at baseline to 299. 07 ± 51.14 μm, 294.70 ± 58.96 μm, and 280.93 ± 53.57 μm at 3, 6, and 12 months after PRP, respectively. However, the choriocapillaris vessel density in both the fovea and parafovea showed no significant differences following PRP. Eyes with advanced DR showed a significant reduction in CVI, L/S ratio, and SFCT over 12 months after PRP treatment.


Critical operational parameters for zero sludge production in biological wastewater treatment processes combined with sludge disintegration.
Mathematical models were developed to elucidate the relationships among process control parameters and the effect of these parameters on the performance of anoxic/oxic biological wastewater processes combined with sludge disintegrators (A/O-SD). The model equations were also applied for analyses of activated sludge processes hybrid with sludge disintegrators (AS-SD). Solubilization ratio of sludge in the sludge disintegrator, alpha, hardly affected sludge reduction efficiencies if the biomass was completely destructed to smaller particulates. On the other hand, conversion efficiency of non-biodegradable particulates to biodegradable particulates, beta, significantly affected sludge reduction efficiencies because beta was directly related to the accumulation of non-biodegradable particulates in bioreactors. When 30% of sludge in the oxic tank was disintegrated everyday and beta was 0.5, sludge reduction was expected to be 78% and 69% for the A/O-SD and AS-SD processes, respectively. Under this condition, the sludge disintegration number (SDN), which is the amount of sludge disintegrated divided by the reduced sludge, was calculated to be around 4. Due to the sludge disintegration, live biomass concentration decreased while other non-biodegradable particulates concentration increased. As a consequence, the real F/M ratio was expected to be much higher than the apparent F/M. The effluent COD was maintained almost constant for the range of sludge disintegration rate considered in this study. Nitrogen removal efficiencies of the A/O-SD process was hardly affected by the sludge disintegration until daily sludge disintegration reaches 40% of sludge in the oxic tank. Above this level of sludge disintegration, autotrophic biomass concentration decreases overly and TKN in the effluent increases abruptly in both the A/O-SD and AS-SD processes. Overall, the trends of sludge reduction and effluent quality according to operation parameters matched well with experimental results found in literatures.


Clinical evaluation of single 4-mm implants in the posterior mandible: A 3-year follow-up pilot study.
Extra-short implants in the posterior mandible can increase the functional surface area and reduce the risk of implant overload. However, reports of treatment using single extra-short implants in the posterior mandible with a midterm follow-up are lacking. The purpose of this prospective pilot study was to evaluate the clinical behavior of single extra-short 4-mm implants placed in the posterior mandible during a follow-up of 3 years from implant restoration. A total of 18 participants with a single extra-short 4-mm-long implant placed in the area of the mandibular first molars participated in this pilot study. The survival and success rates of implants, as well as biologic and prosthetic variables, were evaluated during a follow-up of 3 years from implant restoration. The survival rate of the implants was 100%, with no implant or biologic complications recorded. One prosthetic complication (loosening of 1 screw) was observed. Single extra-short (4 mm) implants in the posterior mandible showed favorable clinical behavior during the first 3-years of follow-up.


Predicting unbound phenytoin concentrations in patients receiving valproic acid: a comparison of two prediction methods.
To compare the predictive performance of 2 equations that estimate unbound (free) phenytoin plasma concentrations when valproic acid (VPA) and phenytoin are administered concurrently. Eighty-eight adults receiving VPA and phenytoin concurrently were included in the study. Steady-state plasma concentration measurements of total phenytoin, total VPA, and unbound phenytoin were collected prospectively in the inpatient group (group 1) and retrospectively in the outpatient group (group 2). Using the equations developed by Haidukewych and May, unbound phenytoin concentrations were calculated. The mean predicted unbound phenytoin concentrations then were compared with mean actual unbound phenytoin concentrations measured in the laboratory. Identical assays were performed to measure unbound phenytoin, total phenytoin, and VPA from each patient group. Antiepileptic drug concentration measurements were collected from 43 inpatients (mean age 34.8 y) from the epilepsy unit at Abbott Northwestern Hospital and 45 outpatients (mean age 37.3 y) at the MINCEP Epilepsy Care clinic, Minneapolis, MN. Mean prediction error (MPE) and mean squared error (MSE) were calculated to determine which equation was the least biased and most precise in predicting unbound phenytoin when total VPA and phenytoin concentrations are known. Linear regression of predicted unbound phenytoin on measured unbound phenytoin values determined the correlation coefficients (r). A paired Student's t-test also was performed comparing mean predicted unbound phenytoin concentration with mean actual unbound phenytoin concentrations in both groups. The MPE from May's equation was -0.49 and -0.45 for groups 1 and 2, respectively; using the Haidukewych equation, MPE was -0.02 and 0.08 for groups 1 and 2, respectively. The MSE using May's equation was 0.34 for both groups. Using the Haidukewych equation, group 1 MSE was 0.07, and for group 2, 0.12. Correlation coefficients were more than 0.91 (p < 0.001) from each equation in both patient groups. In group 1, mean actual unbound phenytoin concentration was 2.02 micrograms/mL; May's equation predicted 1.52 micrograms/mL (p < 0.001) and the Haidukewych equation predicted 2.00 micrograms/mL (p = 0.64). In group 2, mean actual unbound phenytoin concentration was 2.10 micrograms/mL; May's equation predicted 1.65 micrograms/mL (p < 0.001) and the Haidukewych equation predicted 2.18 micrograms/mL (p = 0.11). Haidukewych's equation predicts unbound phenytoin concentrations with the least bias and most precision with statistical significance. May's equation consistently underpredicted unbound phenytoin concentrations. Because unbound phenytoin fraction is not constant (and usually more than the expected 10%) in patients comedicated with VPA, unbound phenytoin concentrations cannot be predicted even though total VPA and phenytoin concentrations are known. If unbound phenytoin concentrations cannot be readily measured, Haidukewych's equation is a reliable predictor of unbound phenytoin concentrations.


Determinants of quality of life in Marfan syndrome.
Marfan syndrome (MFS) is a rare, heritable disorder that affects connective tissue. Men and women are equally affected. Clinical manifestations involve multiple sites, especially bones and ligaments and heart and blood vessels. Authors sought to investigate quality of life (QoL) in MFS patients, assessing positive and negative sociodemographic factors and self-perceived well-being and functional status. Thirty-six patients affected by MFS were interviewed and were administered the SF-36 psychometric questionnaire. Subjects affected by MFS reported an impaired quality of life in the psychological domain but not in the physical domain, as compared with a healthy population. Being male and older was significantly associated with a poorer perceived mental QoL. The authors found that MFS negatively influences QoL, increases psychological distress, and may be a possible risk for some psychiatric disorders.


Accuracy of the tongue blade test in patients with suspected mandibular fracture.
The inter-observer reliability and accuracy of the tongue blade test (TBT) for the identification of patients with mandibular fracture was prospectively evaluated using radiographic diagnosis as the gold standard. A consecutive sample of 110 patients presenting to the emergency department of a teaching county hospital was studied. Patients with uninterpretable x-rays, known diagnosis of mandibular fracture, or inability to cooperate for the test were excluded. Bilateral ability to crack a wooden tongue blade held between the teeth was scored as a negative test. Fifty-three patients had mandibular fractures. In the study group, the TBT had a sensitivity of 95.7%; a specificity of 63.5%; a positive predictive value of 66.2%; a negative predictive value of 95.2%; and an accuracy of 77.3%. The TBT provided contributory evidence useful in screening patients for mandibular fracture.


Appendiceal adenocarcinoma: long-term outcomes after surgical therapy.
Appendiceal adenocarcinomas are very rare. We analyzed contemporary outcomes associated with surgical therapies for these malignancies. Retrospective outcomes for patients treated at a tertiary academic medical center from 1981 through 2001 were analyzed. A total of 36 patients (22 females (61 percent) mean age, 52 years) with appendiceal adenocarcinoma were treated. Eighty-eight percent of patients presented with symptoms of acute appendicitis. Eighteen (50 percent) patients underwent curative resection (7 primary right hemicolectomies, 10 appendectomies + subsequent right hemicolectomy, and 1 appendectomy alone). Mean length of follow-up was 55 months. Overall five-year survival rate was 46 percent. The five-year survival rate after curative resection was 61 percent and after palliative surgery was 32 percent ( P < 0.05). Among patients who underwent curative resection, factors associated with improved five-year survival rates included histologic type (79 vs. 32 percent for colonic vs. mucinous types, respectively; P < 0.05), T stage (75 vs. 47 percent for T1 and 2 vs. T3 and 4, respectively; P < 0.05), and tumor grade (100 vs. 46 percent for well-differentiated tumors vs. moderately or poorly differentiated tumors, respectively; P < 0.05). Patients undergoing surgery for appendiceal adenocarcinoma can be stratified according to prognostic variables. The role of adjuvant therapies for patients with poor prognostic factors needs to be evaluated in a multi-institutional setting.


Effects of ivermectin and midecamycin on ryanodine receptors and the Ca2+-ATPase in sarcoplasmic reticulum of rabbit and rat skeletal muscle.
1. Ryanodine receptor (RyR) Ca2+ channels in the sarcoplasmic reticulum (SR) of skeletal muscle are regulated by the 12 kDa FK506- (or rapamycin-) binding protein (FKBP12). Rapamycin can also activate RyR channels with FKBP12 removed, suggesting that compounds with macrocyclic lactone ring structures can directly activate RyRs. Here we tested this hypothesis using two other macrocyclic lactone compounds, ivermectin and midecamycin. 2. Rabbit skeletal RyRs were examined in lipid bilayers. Ivermectin (cis, 0.66-40 microM) activated six of eight native, four of four control-incubated and eleven of eleven FKBP12-'stripped' RyR channels. Midecamycin (cis, 10-30 microM) activated three of four single native channels, six of eight control-incubated channels and six of seven FKBP12-stripped channels. Activity declined when either drug was washed out. 3. Neither ivermectin nor midecamycin removed FKBP12 from RyRs. Western blots of terminal cisternae (TC), incubated for 15 min at 37 C with 40 microM ivermectin or midecamycin, showed normal amounts of FKBP12. In contrast, no FKBP12 was detected after incubation with 40 microM rapamycin. 4. Ivermectin reduced Ca2+ uptake by the SR Ca2+-Mg2+-ATPase. Ca2+ uptake by TC fell to approximately 40% in the presence of ivermectin (10 microM), both with and without 10 microM Ruthenium Red. Ca2+ uptake by longitudinal SR also fell to approximately 40% with 10 microM ivermectin. Midecamycin (10 microM) reduced Ca2+ uptake by TC vesicles to approximately 76% without Ruthenium Red and to approximately 90 % with Ruthenium Red. 5. The rate of rise of extravesicular [Ca2+] increased approximately 2-fold when 10 microM ivermectin was added to TC vesicles that had been partially loaded with Ca2+ and then Ca2+ uptake blocked by 200 nM thapsigargin. Ivermectin also potentiated caffeine-induced Ca2+ release to approximately 140% of control. These increases in Ca2+ release were not seen with midecamycin. 6. Ivermectin, but not midecamycin, reversibly reduced Ca2+ loading in four of six skinned rat extensor digitorum longus (EDL) fibres to approximately 90%, and reversibly increased submaximal caffeine-induced contraction in five of eight fibres by approximately 110% of control. Neither ivermectin nor midecamycin altered twitch or tetanic tension in intact EDL muscle fibres within 20 min of drug addition. 7. The results confirm the hypothesis that compounds with a macrocyclic lactone ring structure can directly activate RyRs. Unexpectedly, ivermectin also reduced Ca2+ uptake into the SR. These effects of ivermectin on SR Ca2+ handling may explain some effects of the macrolide drugs on mammals.


Distribution, fate, and risk assessment of antibiotics in five wastewater treatment plants in Shanghai, China.
The project studied the occurrence, fate, and seasonal variation of 14 antibiotics, from five wastewater treatment plants (WWTPs) in Shanghai. The results indicated that ofloxacin, sulfamethoxazole, and oxytetracycline were the predominant antibiotics, with maximum concentrations of 1208.20, 959.13, and 564.30 ng/L in influents, while 916.88, 106.60, and 337.81 ng/L in effluents, respectively. The level of antibiotics in WWTPs obviously varied with seasonal changes, and higher detectable frequencies and concentrations were found in winter. The daily mass loads per capita of amoxicillin, enrofloxacin, and oxytetracycline in the study were all higher than those in other regions/countries, such as Hong Kong, Australia, and Italy. The elimination of antibiotics through these WWTPs was incomplete, and a wide range of removal efficiencies during the different treatment process and seasons were observed (-500.56 to 100 % in winter and -124.24 to 94.21 % in summer). Sulfonamides were relatively easy to be removed in WWTPs and the ultraviolet (UV) process can effectively improve the removal efficiency. Risk assessment of antibiotics in effluents was estimated. Only AMOX's hazard quotient (HQ) was higher than 0.01. Even though the environmental risks in the study were estimated to be low, the potential negative effects on aquatic ecosystems should call our attention as continually discharge in the long term.


Recurring loop motif in proteins that occurs in right-handed and left-handed forms. Its relationship with alpha-helices and beta-bulge loops.
A common feature of alpha-helices in proteins is a loop at the C-terminal end, with a characteristic hydrogen bond pattern. It is noted that several loops with the same structural features occur independently of alpha-helices; two are even situated at the loop ends of beta-hairpins. The name paperclip is suggested for loops possessing the appropriate hydrogen bonds. A number of features of paperclips are described: they exist in two classes, depending on the number of residues at the loop end; one class is very much commoner than the other. Two paperclips are found that belong to the common class, except that the main-chain conformation of each is the mirror image of that normally found. The majority of paperclips are shown to have tightly clustered sets of main-chain dihedral angles. These are somewhat similar to, but distinct from, a subgroup of another common family of loops that have been called beta-bulge loops; in the latter, the dihedral angles are also tightly clustered. The high degree of clustering in both cases is likely to be a result of steric constraints associated with hydrogen bond patterns at the ends of loops.


Pediatric HIV Disclosure Intervention Improves Immunologic Outcome at 48 Weeks: The Sankofa Trial Experience.
The World Health Organization recommends disclosure of HIV status to children and adolescents living with HIV (CALWH). HIV disclosure improves adherence to antiretroviral therapy and immunologic and virologic outcomes. However, the prevalence of HIV disclosure is low in sub-Saharan Africa. We assessed the longitudinal effect of the Sankofa Pediatric HIV disclosure intervention on immunologic and virologic outcomes among CALWH in Ghana. We conducted a secondary analysis of a two-arm site-randomized clinical trial among CALWH aged 7-18 years. Data were collected at baseline, 24, and 48 weeks. Generalized linear mixed models were used to compare immunologic (CD4) and virologic (viral load) outcomes as both continuous and categorical variables by disclosure status and by intervention group. Among participants who had their HIV status disclosed during this study, the proportion with CD4 percent >25% increased from 56.5% at baseline to 75.4% at week 48 ( P = 0.03), with a slight increase in the undisclosed group (69.5% vs. 74.3%, P = 0.56). In the intervention arm, there was a steady increase in proportion with CD4 percent >25% from 47.1% at baseline to 67.8% at week 48 ( P = 0.01) while it remained unchanged in the control arm (80.5% vs. 81.3% [ P = 0.89]). Concurrently, declines in detectable viral load were observed in both disclosed (63.3% vs. 51.5%, P = 0.16) and undisclosed (69.9% vs. 62.0%, P = 0.17) groups while the intervention group experienced a meaningful drop from 72.9% to 57.6% at 24 weeks ( P = 0.04), which was maintained at 48 weeks. A structured, culturally relevant disclosure intervention can improve clinical outcomes.


Neuroendocrine Carcinoma of the Extrahepatic Bile Ducts: A Case Report.
BACKGROUND Neuroendocrine tumors (NETs) primarily originating from the extrahepatic biliary (EB) tree are a medical rarity, accounting for less than 100 recorded instances globally. This case report outlines an encounter with this uncommon condition, demonstrating the complexities of diagnosis and management. CASE REPORT A 42-year-old woman presented at our Emergency Department with a 3-week history of itching and symptoms of obstructive jaundice. Initial laboratory tests showed hyperbilirubinemia and elevated liver transaminases. Abdominal ultrasonography indicated choledocholithiasis. Magnetic resonance imaging suggested either Mirizzi syndrome or a proximal common bile duct neoplasm. Abdominal computed tomography showed cholestasis, suggesting choledocholithiasis or cholangiocarcinoma (type-1). An endoscopic retrograde cholangiopancreatography with biliary and pancreatic duct stenting was performed for drainage, with brush cytology confirming adenocarcinoma. The patient was referred for surgical resection of the bile duct tumor, involving extrahepatic bile duct resection, en bloc cholecystectomy, lymphadenectomy, Roux-en-Y anastomosis, and biliary drainage. Histopathology identified a neuroendocrine carcinoma. Following surgery, the patient underwent eight cycles of FOLFOX6 chemotherapy, with no disease relapse post-treatment. CONCLUSIONS This case emphasizes multidisciplinary teamwork importance in managing rare diseases like EB bile duct NETs. These tumors' rarity and symptom ambiguity necessitate histological examination for accurate diagnosis. This report aims to guide healthcare professionals facing similar future cases.


Avoidance of all feedback? Attention allocation during and after public speech in social anxiety.
Attention avoidance of feedback-related stimuli is proposed to be associated with and maintain social anxiety. However, previous research has mainly focused on comparing the attention bias between two types of stimuli, while little is known about attention distribution patterns among positive, neutral, and negative feedback and non-feedback stimuli in individuals with high trait social anxiety (HSA) or low trait social anxiety (LSA). The current study assessed eye movement pattern of participants with HSA or LSA during a speech task (high anxiety condition) or while solely watching audience feedback of the speech (low anxiety condition). A pre-recorded audience who displayed approving, neutral, or disapproving gestures was presented as feedback stimuli, while neutral facial photos were used as non-feedback stimuli. Only in the high anxiety condition, participants with HSA exhibited longer total fixation on non-feedback stimuli compared to those with LSA; whereas in the low anxiety condition, both groups paid more attention to emotional feedback stimuli. The final sample size was modest due to a high suspicion rate of the reality of the audience. These findings suggest that only in highly anxious social situations, socially anxious individuals lack the attentional preference toward positive feedback that individuals with low anxious have.


Kinetic properties of the sodium-calcium exchanger in rat brain synaptosomes.
1. The kinetic properties of the internal Na+ (Na+i)- dependent 45Ca2+ influx and external Na+ (Na+o)-dependent 45Ca2+ efflux were determined in isolated rat brain nerve terminals (synaptosomes) under conditions which the concentrations of internal Na+ ([Na+]i), external Na+ ([Na+]o), external Ca2+ (Ca2+]o), and external K+ ([K+]o) were varied. Both fluxes are manifestations of Na(+)-Ca2+ exchange. 2. Ca2+ uptake was augmented by raising [Na+]i and / or lowering [Na+]o. The increase in Ca2+ uptake induced by removing external Na+ was, in most instances, quantitatively equal to the Na+i-dependent Ca2+ uptake. 3. The Na+i-dependent Ca2+ uptake (measured at 1 s) was activated with an apparent half-maximal [Ca2+]o (KCa(o)) of about 0.23 mM. External Na+ inhibited the uptake in a non- competitive manner: increasing [Na+]o from 4.7 to 96 mM reduced the maximal Na+(i)-dependent Ca2+ uptake but did not affect KCa(o). 4. The inhibition of Ca2+ uptake by Na+o was proportional to ([Na+]o)2, and had a Hill coefficient (nH) of approximately 2.0. The mean apparent half-maximal [Na+]o for inhibition (KI(Na)) was about 60mM, and was independent of [Ca2+]o between 0.1 and 1.2mM; this, too, is indicative of non-competitive inhibition. 5. Low concentrations of alkali metal ions (M+) in the medium, including Na+, stimulated the Na+i-dependent uptake. The external Na+ and K+ concentrations required for apparent half-maximal activation (KM(Na) and KM(K), respectively) were 0.12 and 0.10mM. Thus, the relationship between Ca2+ uptake and [Na+]o was biphasic: uptake was stimulated by [Na+]o < or = 10 mM, and inhibited by higher [Na+]o. 6. The calculated maximal Na+i-dependent Ca2+ uptake (Jmax) was about 1530 pmol (mg protein) -1s-1 at 30 degrees C saturating [Ca2+]o and external M+ concentration ([M+]o), and with negligible inhibition by external Na+. 7. Internal Na+ activated the Ca2+ uptake with an apparent half-maximal concentration (KNa(i)) of about 20 mM and a Hill coefficient, nH, of approximately 3.0. 8. The Jmax for the Na+o-dependent efflux of Ca2+ from 45Ca(2+)-loaded synaptosomes treated with carbonyl cyanide p-trifluormethoxy-phenylhydrazone (FCCP) and caffeine (to release stored Ca2+ and raise the internal Ca2+ concentration ([Ca2+]i) was about 1800-2000 pmol (mg protein -1s-1 at 37 degrees C. 9. When the membrane potential (Vm) was reduced (depolarized) by increasing [K+]o, the Na+i-dependent Ca2+ influx increased, and the Na+o-dependent Ca2+ efflux declined. Both fluxes changed about 2-fold per 60 mV change in Vm. This voltage sensitivity corresponds to the movement of one elementary charge through about 60% of the membrane electric field. The symmetry suggests that the voltage-sensitive step is reversible. 10. The Jmax values for both Ca2P influx and efflux correspond to a Na+-Ca2+ exchange-mediated flux of about 425-575 jumol Ca2P (1 cell water)-' s-' or a turnover of about one quarter of the total synaptosome Ca2P in 1 s. We conclude that the Na+-Ca2P exchanger may contribute to Ca2P entry during nerve terminal depolarization; it is likely to be a major mechanism mediating Ca2P extrusion during subsequent repolarization and recovery.


FACTORS ASSOCIATED WITH PREVALENT LENS OPACITIES IN CHINESE AMERICAN ADULTS: THE CHINESE AMERICAN EYE STUDY.
To identify risk factors associated with lens opacities in Chinese Americans. A cross-sectional population-based study of 4,582 Chinese Americans ≥50 years residing in Monterey Park, California. Participants completed a comprehensive clinical examination with lens assessment using the Lens Opacities Classification System II, with lens opacities defined by a grade ≥2 in either eye. Participants were considered to have nuclear-only, cortical-only, or posterior subcapsular (PSC)-only if that was the only type of opacity present in both eyes. Cortical-only opacity was associated with older age, diabetes mellitus (OR 1.5, 95%CI 1.1-2.1), and family history of cataracts (OR 1.5, 95%CI 1.2-1.9). Nuclear-only opacity was associated with older age, diabetes mellitus (OR 1.4, 95%CI 1.1-1.9), greater waist-to-hip ratio (OR 1.2, 95%CI 1.1-1.4), and high-density lipoprotein (OR 1.1, 95%CI 1.02-1.2). Mixed-type opacities were associated with older age, greater waist-to-hip ratio (OR 1.3, 95%CI 1.1-1.6), and higher HbA1 c (OR 1.3, 95%CI 1.1-1.4). Taller height (OR 0.7, 95%CI 0.6-0.8), greater weight (OR 0.98, 95%CI 0.97-0.99), and higher diastolic pressure (OR 0.98, 95%CI 0.96-0.99) were protective. CHES identified a strong, dose-response association between age and all types of prevalent lens opacities, which suggests an increasing cataract burden in Chinese Americans based on aging populations. CHES results demonstrate general consistency with previous population-based studies in regard to more sedentary lifestyle exposures (e.g., Westernized lifestyle) and prevalent cortical-only, nuclear-only, and mixed-type opacities, yet also identified further sedentary lifestyle exposures associated with prevalent lens opacities. Improved glycemic control and a more active lifestyle that minimizes factors contributing to metabolic syndrome may help reduce the burden of vision loss associated with lens opacities.


Phenoxybenzamine in neurogenic bladder dysfunction after spinal cord injury. II. Autonomic dysreflexia.
Phenoxybenzamine blockade of the alpha receptor site can abolish the vascular and internal sphincter responses in patients with chronic recurrent autonomic dysreflexia associated with bladder filling or contraction. The life-threatening hypertensive response is suppressed by this medication. Therefore, the drug is a beneficial adjunct in the pharmacologic management of autonomic dysreflexia. When the drug is used patients can be maintained free of a catheter. The drug had no serious side effects at the dose regimen used. One particularly significant advantage is its long duration of action--patients occasionally can skip doses of medication and not suffer acute symptoms.


Associations of 25-hydroxyvitamin D status and vitamin D supplementation use with mortality due to 18 frequent cancer types in the UK Biobank cohort.
Although the associations of serum 25-hydroxyvitamin D (25(OH)D) levels and vitamin D supplementation with total cancer mortality are well-known, evidence regarding the association of 25(OH)D and cancer site-specific mortality is predominantly limited to common cancer types, and most studies on vitamin D supplementation use have limitations on sample size and the adjustment of important confounding factors. We used cause-specific Cox regression models adjusted for 48 covariates to assess the associations of vitamin D deficiency, insufficiency, and vitamin D supplementation use with mortality from any cancer and 18 specific cancers in 411,436 United Kingdom Biobank participants, aged 40-69 years. The majority of the study population had either vitamin D deficiency (21.1%) or insufficiency (34.4%). Furthermore, 4.1% and 20.3% of the participants regularly took vitamin D or multivitamin supplements, respectively. During a median follow-up of 12.7 years, vitamin D deficiency was associated with significantly increased mortality from total cancer and four specific cancers: stomach (hazard ratio, 95% confidence interval: 1.42, 1.05-1.92), colorectal (1.27, 1.07-1.50), lung (1.24, 1.10-1.40), and prostate (1.36, 1.06-1.75). Vitamin D insufficiency was associated with increased colorectal (1.14, 1.00-1.30) and lung cancer mortality (1.19, 1.08-1.32). Compared to non-users, vitamin D use was associated with lower lung cancer (0.75, 0.60-0.95) and total cancer mortality. Multivitamin use was associated with lower mortality from melanoma (0.64, 0.43-0.97). Vitamin D deficiency and insufficiency were associated with increased mortality from multiple common cancers. The potential to reduce cancer mortality by vitamin D supplementation in populations with low 25(OH)D levels should be further explored.


Digital codes from hypervariable tandemly repeated DNA sequences in the Plasmodium falciparum circumsporozoite gene can genetically barcode isolates.
DNA typing systems currently used in parasitology involve either hybridising Southern blots with repetitive sequence probes or amplifying genomic sequences using the polymerase chain reaction (PCR). Both such approaches assay allelic length variation, usually in unexpressed tandemly repeated DNA sequences. Where an appropriate target locus exists, an alternative PCR-based strategy which reveals allelic sequence variation in tandemly repeated DNA offers a more accurate and internally controlled assay. We describe such a strategy for the rapid extraction of information on tandem repeat sequence variation from hypervariable alleles, and apply it to the Plasmodium falciparum CS gene. The extreme variability of such DNA 'barcodes' can be used to identify parasite stocks and lineages. This system is also potentially useful for population genetic and epidemiological studies since it offers the possibility of following the spread of distinctively marked parasite genotypes in samples taken from infected individuals.


A case of unicuspid aortic valve associated with a single coronary artery and ventricular septal defect.
The patient was a 26-year-old man who had undergone patch closure of a ventricular septal defect at 2 years of age. After this surgery, his condition was satisfactory until he visited our hospital for treatment of paroxysmal supraventricular tachycardia in November 2000. Echocardiography revealed moderate to severe aortic valve regurgitation and dilatation of the left ventricle and ascending aorta. These echocardiographic abnormalities were attributed to a bicuspid aortic valve. Coronary angiography suggested the presence of a single coronary artery originating from the left Valsalva sinus. We performed Bentall's operation in January 2003. The intraoperative findings revealed that the aortic valve consisted of an extensively calcified single cusp, and there was a single coronary artery originating from the left Valsalva sinus. Because adult patients with a unicuspid aortic valve are rare, and no cases of unicuspid aortic valve associated with a single coronary artery have been reported, we herein report this case with a review of the literature.


Heterogeneous HBV mutants coexist in Korean hepatitis B patients.
Although many hepatitis B virus (HBV) mutants have been found in all open reading frames since the precore defective mutant was initially reported, systematic investigations of diverse HBV mutant populations in hepatitis B patients have not been performed. Therefore, we examined whether heterogeneous mutant populations simultaneously exist in Korean hepatitis B patients. In order to detect hepatitis B virus mutants, we amplified a conserved core region and a surface antigen region of HBV DNA by PCR from sera of 27 Korean chronic hepatitis B patients, and then performed single strand conformational polymorphism analysis followed by DNA sequencing analysis. The results showed that heterogeneous HBV mutants in both regions were present in a single as well as in various hepatitis B patients. Sequence analysis revealed a defective interfering particle with missense mutation in the core region. We also found that two subtypes of adr and adw coexisted in a single patient. In addition, a point mutation causing a stop codon in the surface antigen region was observed. We are further analyzing the clinical implications of HBV mutants to identify their roles in the pathogenesis of chronic hepatic disorders induced by HBV.


Synthesis of norlignans and in vitro inhibitory activity of antigen-induced degranulation.
The synthesis and biological evaluation of a series of novel norlignans are described. Norlignans were evaluated for their inhibitory activity on the release of β-hexosaminidase, a marker of degranulation, from RBL-2H3 cells induced by the IgE-antigen complex. The results showed that norlignans 4c and 4e potently inhibited degranulation, with IC(50) values of 18.3 and 17.9 μM, respectively.


RNA-based vaccines.
Nucleic acid vaccines consisting of plasmid DNA, viral vectors or RNA may change the way the next generation vaccines are produced, as they have the potential to combine the benefits of live-attenuated vaccines, without the complications often associated with live-attenuated vaccine safety and manufacturing. Over the past two decades, numerous clinical trials of plasmid DNA and viral vector-based vaccines have shown them to be safe, well-tolerated and immunogenic. Yet, sufficient potency for general utility in humans has remained elusive for DNA vaccines and the feasibility of repeated use of viral vectors has been compromised by anti-vector immunity. RNA vaccines, including those based on mRNA and self-amplifying RNA replicons, have the potential to overcome the limitations of plasmid DNA and viral vectors. Possible drawbacks related to the cost and feasibility of manufacturing RNA vaccines are being addressed, increasing the likelihood that RNA-based vaccines will be commercially viable. Proof of concept for RNA vaccines has been demonstrated in humans and the prospects for further development into commercial products are very encouraging.


Variation of muscle recruitment during exercises performed below horizontal arm elevation that target the lower trapezius: A repeated measures cross-sectional study on asymptomatic individuals.
The gold standard exercise for recruitment of the lower trapezius is the Y prone exercise which is performed above 90° of shoulder elevation. However, clinicians often prescribe exercises that avoid high elevation postures during early stages of rehabilitation. Comparatively little data exists on relative muscle recruitment during lower arm elevation exercises. This study examined the EMG activity of four shoulder girdle muscles during four exercises accomplished below 90° of shoulder elevation and compared them to the Y prone while considering sex effects. Variance across exercises of the ratio between upper trapezius and lower trapezius was also explored. 32 healthy participants completed standardized muscle-specific MVCs and two repetitions of each exercise. The side lying external rotation and the wall slide exercises produced the highest peak EMG for the lower trapezius, both 33 and 29% lower than the Y Prone. For the upper trapezius to lower trapezius ratio, the side lying external rotation elicited the lowest value, followed by the Y prone and wall slide (53 and 59% respectively higher). Sex influenced some EMG values, typically interacting with exercise type. Thus, side lying external rotation and the wall slide are recommended for targeting the lower trapezius muscle during early rehabilitation.


The changes in hematocrit, hemoglobin, plasma volume and proteins during and after different types of exercise.
A group of 7 healthy males was studied after maximal exercise and during and after prolonged exercise of two types (approximately at 40 and 67% of their VO2 max). Hematocrit, plasma proteins concentration, and hemoglobin were followed. Relative changes of plasma volume and total content of plasma protein were calculated from hematocrit changes. The mean corpuscular hemoglobin concentration was obtained by dividing hemoglobin by hematocrit. After maximal exercise, hemoconcentration with concomitant decrease of plasma volume (-13.0%) was found, with a corresponding increase in protein concentration (+12.9%) and without any protein content changes. Later normalisation at the 30th min of the recovery phase was shown. During prolonged submaximal exercise (67% of VO2 max) the changes in hemoconcentration, plasma volume (-7.1%), and plasma protein concentration (+6.9%) reached the highest changes in the first 15 min of exercise, and no decrease in protein content was observed. After them the spontanious tendency to the normalisation was found. No changes were registered in prolonged mild exercise (40% of VO2 max). The ratio of hemoglobin to hematocrit remained unchanged during and after all types of exercise.


The structure and function of endovascular stents: a primer for the interventional nephrologist.
The use of stents has become common practice in various interventional fields. The purpose of this article is to provide the interventionalist with an understanding of the basic structure stent. We describe the etymology, the classification and describe various terms used by engineers as they strive to develop that "ideal" stent. We also describe the fabrication process briefly and finally elaborate on the characteristic "build and cut" of some commonly used stents.


Hierarchically porous carbons as supports for fuel cell electrocatalysts with atomically dispersed Fe-N x moieties.
The development of high-performance non-platinum group metal (non-PGM) catalysts for the oxygen reduction reaction (ORR) is still of significance in promoting the commercialization of proton exchange membrane fuel cells (PEMFCs). In this work, a "hierarchically porous carbon (HPC)-supporting" approach was developed to synthesize highly ORR active Fe-phenanthroline (Fe-phen) derived Fe-N x -C catalysts. Compared to commercial carbon black supports, utilizing HPCs as carbon supports can not only prevent the formation of inactive iron nanoparticles during pyrolysis but also optimize the porous morphology of the catalysts, which eventually increases the amount of reactant-accessible and atomically dispersed Fe-N x active sites. The prepared catalyst therefore exhibits a remarkable ORR activity in both half-cells (half-wave potential of 0.80 V in 0.5 M H2SO4) and H2-air PEMFCs (442 mA cm-2 at a working voltage of 0.6 V), making it among the best non-PGM catalysts for PEMFCs.


Thiol-reactive reagents inhibits intracellular trafficking of human papillomavirus type 16 pseudovirions by binding to cysteine residues of major capsid protein L1.
A human papillomavirus (HPV) virion is composed of capsid proteins L1 and L2. Several cysteine residues are located on L1 of various HPVs at markedly similar relative positions, suggesting their important functions. Although the authentic virions cannot be studied with cultured cells, surrogate pseudovirions consisting of capsid and reporter plasmid are available for studies dealing with infectivity. HPV type16-pseudovirions (16PVs) were found to lose their infectivity after incubation with thiol-reactive reagents [biotin polyethyleneoxide iodoacetamide (BPEOIA), 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), N-ethylmaleimide (NEM), 4-(N-maleimido)benzyl-trimethylammonium iodide (MBTA), and [2-(trimethylammonium)ethyl] methanethiosulfonate bromide (MTSET)]. A labelled streptavidin was detected to bind to the complex of BPEOIA and L1 of the 16PVs incubated with BPEOIA. The analysis of molecular mass of trypsin-fragments derived from the complex of the BPEOIA and L1 indicated that BPEOIA bound to at least C146, C225, and C229. No appreciable change of the 16PVs carrying DTNB or NEM was detected by sedimentation analysis or electron microscopy. The 16PVs carrying DTNB or NEM were able to bind to and enter HeLa cells but degraded before they reached the perinuclear region. HPV16 L1 C146, C225, and C229 have free thiol, which are accessible to BPEOIA, DTNB, NEM, MBTA, and MTSET. Binding of DTNB or NEM to the thiols may cause conformational changes that result in the inhibition of the entry and trafficking of the 16PVs.


Diagnostic accuracy of microEEG: a miniature, wireless EEG device.
Measuring the diagnostic accuracy (DA) of an EEG device is unconventional and complicated by imperfect interrater reliability. We sought to compare the DA of a miniature, wireless, battery-powered EEG device ("microEEG") to a reference EEG machine in emergency department (ED) patients with altered mental status (AMS). Two hundred twenty-five ED patients with AMS underwent 3 EEGs. Two EEGs, EEG1 (Nicolet Monitor, "reference") and EEG2 (microEEG) were recorded simultaneously with EEG cup electrodes using a signal splitter. The remaining study, EEG3, was recorded with microEEG using an electrode cap immediately before or after EEG1/EEG2. The official EEG1 interpretation was considered the gold standard (EEG1-GS). EEG1, 2, and 3 were de-identified and blindly interpreted by two independent readers. A generalized mixed linear model was used to estimate the sensitivity and specificity of these interpretations relative to EEG1-GS and to compute a diagnostic odds ratio (DOR). Seventy-nine percent of EEG1-GS were abnormal. Neither the DOR nor the κf representing interrater reliabilities differed significantly between EEG1, EEG2, and EEG3. The mean setup time was 27 min for EEG1/EEG2 and 12 min for EEG3. The mean electrode impedance of EEG3 recordings was 12.6 kΩ (SD: 31.9 kΩ). The diagnostic accuracy of microEEG was comparable to that of the reference system and was not reduced when the EEG electrodes had high and unbalanced impedances. A common practice with many scientific instruments, measurement of EEG device DA provides an independent and quantitative assessment of device performance.


[Complications and results of diagnostic procedures in the vena cava superior syndrome].
Diagnostic procedures in the presence of superior vena cava obstruction have been reported to be dangerous. We reviewed our experience in 58 patients who presented with this obstruction during the period 1976-1985, to establish the nature and frequency of complications. In 56 of 58 patients we could obtain a diagnosis before instituting therapy. The only complication was one case of peroperative haemorrhage.


[RARE COMPLICATION OF PANCREATITIS PANKREATOPLEVRALNY FISTULA BOTH PLEURAL CAVITY].
This article presents a case of a rare complication--pankreatopleural fistula in a patient with chronic pancreatitis. The features of clinical manifestations and complications of this diagnostic search.


Differential regulation of alpha- and beta-CGRP mRNAs within oculomotor, trochlear, abducens, and trigeminal motoneurons in response to axotomy.
Spinal and cranial motoneurons express alpha- and beta-calcitonin gene-related peptide (CGRP) mRNAs constitutively at variable ratios, and these two mRNAs are differentially regulated following axotomy in spinal, facial, and hypoglossal motoneurons. The purpose of this study was to investigate the change in CGRP mRNA expression following nerve injury in oculomotor, trochlear, abducens, and trigeminal motor nuclei in which beta-CGRP mRNA is predominantly expressed under normal conditions. Using male Sprague-Dawley rats, either the left eyeball and the orbital contents including the bulbar muscles were removed, or the left masseter nerve was ligated and transected. The rats were allowed to survive for 1, 3, 7, 14, 28, 56 days following these procedures. The levels of mRNAs for alpha- and beta-CGRP and growth-associated protein (GAP)-43 were analyzed by in situ hybridization histochemistry using 35S-labeled oligonucleotide probes. Following nerve injury, the expression of alpha-CGRP mRNA rapidly increased on the directly-injured side in all of these nuclei. Thereafter, it gradually decreased and returned to about the control level at postoperative day 56 within oculomotor, trochlear, and abducens motoneurons, but it sustained at a high level within trigeminal motoneurons. The expression of beta-CGRP was quite variable among these nuclei, and significant changes were also seen on the side contralateral to the directly-injured side. These data indicate that the up-regulation of alpha-CGRP mRNA may be a common response of cranial motor neurons following axotomy even if the constitutive expression of beta-CGRP mRNA exceeds that of alpha-CGRP mRNA in these neurons.


Clinical usefulness of microsatellite instability test in Korean young patients with high-risk features associated with adenoma.
The aim of this study was to determine the correlation between microsatellite instability (MSI) and young age in patients with advanced colorectal adenomas. We retrospectively analyzed young patients (≤ 40 years of age) with advanced adenomas (n=84) between January 1996 and December 2006. We randomly selected the control group as patients ≥ 50 years of age with advanced adenomas (n=84) during the same time period. Of these patients, the MSI test and MLH1 immunohistochemistry were performed in the available tissue samples from patients with advanced adenomas. The number of patients who had the two tests was 52 in the young group and 49 in the old group. The monomorphic nature of the BAT26 panel for MSI analysis was used without comparison of normal tissue. MSI was detected in three young patients (n=52) and none of the old patients (n=49). There was no statistical difference between the two groups (P=0.243). All three young patients with MSI had a strong family history of colorectal cancer. MSI analysis was not a useful method of screening for HNPCC in young patients with advanced colorectal adenoma, at least in cases without a family history of colorectal cancer.


Clinical and mutational characteristics of Duchenne muscular dystrophy patients based on a comprehensive database in South China.
The development of clinical trials for Duchenne muscular dystrophy (DMD) in China faces many challenges due to limited information about epidemiological data, natural history and clinical management. To provide these detailed data, we developed a comprehensive database based on registered DMD patients from South China and analysed their clinical and mutational characteristics. The database included DMD registrants confirmed by clinical presentation, family history, genetic detection, prognostic outcome, and/or muscle biopsy. Clinical data were collected by a registry form. Mutations of dystrophin were detected by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Currently, 132 DMD patients from 128 families in South China have been registered, and 91.7% of them were below 10 years old. In mutational detection, large deletions were the most frequent type (57.8%), followed by small deletion/insertion mutations (14.1%), nonsense mutations (13.3%), large duplications (10.9%), and splice site mutations (3.1%). Clinical analysis revealed that most patients reported initial symptoms between 1 and 3 years of age, but the diagnostic age was more frequently between 6 and 8 years. 81.4% of patients were ambulatory. Baseline cardiac assessments at diagnosis were conducted in 39.4% and 29.5% of patients by echocardiograms and electrocardiograms, respectively. Only 22.7% of registrants performed baseline respiratory assessments. A small numbers of patients (20.5%) were treated with glucocorticoids. 13.3% of patients were eligible for stop codon read-through therapy, and 48.4% of patients would potentially benefit from exon skipping. The top five exon skips applicable to the largest group of registrants were skipping of exons 51 (14.8% of total mutations), 53 (12.5%), 45 (7.0%), 55 (4.7%), and 44 (3.9%). In conclusion, our database provided information on the natural history, diagnosis and management status of DMD in South China, as well as potential molecular therapies suitable for these patients. This comprehensive database will promote future experimental therapies in China.


The effects of nasal continuous positive airway pressure and high flow nasal cannula on heart rate variability in extremely preterm infants after extubation: A randomized crossover trial.
NCPAP and High flow nasal cannula (HFNC) are common modes of non-invasive respiratory support used after extubation. Heart rate variability (HRV) has been demonstrated as a marker of well-being in neonates and differences in HRV were described in preterm infants receiving respiratory care. The objective was to investigate the effects of NCPAP and HFNC on HRV after extubation. Randomized crossover trial in infants with birth weight (BW) ≤1250 g after undergoing their first elective extubation. ECG recordings were performed during 45 min while on HFNC and nasal continuous positive airway pressure (NCPAP). Time domain, non-linear, and frequency domain parameters were calculated and compared during HFNC and NCPAP using paired nonparametric tests. A secondary analysis was performed in the subgroup of infants that were successfully extubated. Thirty infants with median [range] gestational age of 27 weeks [24.1-29.3] and BW of 930 g [610-1220] were studied at 5 days [1-39] of age. No differences in HRV parameters were observed between HFNC and NCPAP. In the secondary analysis, infants successfully extubated (n = 27) had a significantly higher HRV during HFNC for some time domain parameters. For instance, the standard deviation of the RR intervals (SDRR) was more likely to be higher during HFNC compared to NCPAP (HFNC: 18/27 vs NCPAP: 9/27, P = 0.017) . During the first hours after extubation, no differences in HRV were detected between HFNC and NCPAP in the overall cohort. However, a significantly higher HRV was noted during HFNC in the subgroup of infants successfully extubated.


Glucose tolerance during anaesthesia and surgery. Comparison of general and extradural anaesthesia.
The effects of general and extradural anaesthesia on glucose tolerance and plasma cortisol concentration in the surgical patient were assessed. Normal glucose tolerance and insulin release were observed under extradural anaesthesia, whereas general anaesthesia produced decreases in both glucose tolerance and insulin release. The plasma cortisol concentration was increased in both groups. These results indicate possible nutritional advantages in conducting surgery under extradural anaesthesia.


Corrigendum: Examining the Conceptual and Measurement Overlap of Body Dissatisfaction and Internalized Weight Stigma in Predominantly Female Samples: A Meta-Analysis and Measurement Refinement Study.
[This corrects the article DOI: 10.3389/fgwh.2022.877554.].


The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.
Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic.


The faith of ilioinguinal nerve after preserving, cutting, or ligating it: an experimental study of mesh placement on inguinal floor.
Postherniorrhaphy chronic pain may be related to the trauma to the regional nerves or prosthetic mesh. This study was aimed to search the objective findings of prosthetic mesh placement on the ilioinguinal nerve in three different nerve treatment patterns with two different mesh types. Thirty New Zealand rabbits were used. Bilateral ilioinguinal nerves were identified. A 2×1 cm standard polypropylene mesh was laid on the nerve on right side, whereas a same sized lightweight polypropylene was applied on the left after three different nerve treatments were carried out. The nerve was completely preserved in the first group [G1], cut by scissors without a further process in the second [G2], and proximal cut end was ligated with 5/0 polyglactin. Three months after the surgery, bilateral nerve samples were taken from the contiguous nerve segment for light microscopy and electron microscopy. Nerve protection could not prevent microscopic changes entirely. Prosthetic mesh itself seemed to cause histopathologic changes. Overall incidence of histopathologic changes in light microscopy, without taking the nerve treatment pattern into account, was somewhat lower at standard mesh side than that of lightweight mesh side. However this difference did not reach the level of significance (P=0.39). When three groups were evaluated in respect to overall nerve damage without paying attention to mesh type, the highest damage rate was observed in G3 (cut and ligate). When each group was compared separately within itself for histopathologic changes, no differences were observed between heavy and light mesh sides in any group. When the microscopic changes were compared in respect to the different nerve treatment patterns on heavyweight mesh side, the rates were 12.5%, 12.5%, and 33.3%, respectively. On lightweight mesh side, all three groups exhibited similar microscopic finding rates, 37.5%, 25.0%, and 33.3%, respectively. Protection of the nerve resulted in virtually zero neuroma formation after two types of mesh use. Surgical trauma to the nerve was observed to have an obvious potential for neuroma formation. Mesh type did not affect the overall neuroma rate within the whole subject pool; both groups displayed same 40% overall neuroma development rate. The neuroma incidence was in 43.8% G2 and 72.2% in G3, however the difference did not attain level of significance (P=0.09). The highest rate was observed when a lightweight mesh was used after dividing and ligating the nerve. Light mesh could not provide a protection in subjects whose nerves were injured during surgery. Ligation of the cut end of the nerve also could not be helpful. Nerve protection still seems to be the best way for a nerve-related complaint-free postoperative period. The merit of nerve end implantation into the muscle should also be reconsidered.


Sensate and insensate in-shoe plantar pressures.
In the individual with loss of protective sensation, the presence of high plantar pressures has been considered a risk factor for the development of plantar ulceration. Previous studies of insensate plantar pressures have measured a limited number of isolated, barefoot steps in a laboratory setting. Such isolated snapshots of barefoot plantar pressures do not give us insight into possible step-to-step variations or what plantar pressures occur when wearing shoes. The purpose of this study was to quantitatively examine and compare in-shoe plantar pressures during continuous walking by normal sensate and diabetic insensate subjects. A portable, insole data-acquisition system was used for pressure measurement during 4 minutes of normal continuous walking. Seven pressure sensors were placed in each insole under posterior and anterior heels, the metatarsal heads, and hallux. Twelve sensate and five insensate subjects were studied. We found that the insensate group had higher plantar pressures under posterior and anterior heels and the first metatarsals compared with the sensate group. From the study of the coefficients of variation, we demonstrated a larger step-to-step variation in plantar pressures for the insensate during continuous walking, suggesting the need for caution in interpreting the data from isolated force plate steps when studying insensate individuals.


[The therapeutic mediation device in the clinic of adolescent action].
The pathologies of the adolescent act illustrate the overflow so characteristic of the "modernity" of a world in perpetual evolution. Through compulsive bodily symptoms that are as noisy as they are enigmatic (self-mutilation, suicide attempts, addictions, fast sex, eating disorders), adolescents are always in search of transitional and containing spaces, which are indispensable for symbolizing and calming destructuring intrapsychic conflicts. Therapeutic mediations, adapted to the different singularities, offer a space through which integration and subjectivation processes are possible.


School-based peer-led diabetes intervention among female adolescents: a cluster randomized trial.
The prevalence of type 2 diabetes is increasing among adolescents and clear strategies are needed to prevent it. The aim of this study was to determine the effect of peer education on knowledge, health beliefs and preventive behaviors of type 2 diabetes in female adolescents. In this cluster randomized trial study, 168 students (84 people in each group) were enrolled. The data collection instrument was a questionnaire of knowledge (30 questions), health beliefs (16 questions) and behavior (20 questions) whose validity and reliability were confirmed. Then eight capable students were chosen as peer educators after being trained. The intervention group received 8 sessions of 90-min education through training, lectures, question and answer, and group discussion and with teaching aids such as pamphlets, educational clips and text messages. The post-test was administered two months after the treatment. Data collected using software SPSS16 and Chi-Square and ANCOVA test were used. The result showed that the mean and standard deviation of general knowledge, disease symptoms, behavioral risk factors, mid-term outcomes and long-term outcomes, perceived self-efficacy, behavioral beliefs, perceived susceptibility, perceived severity, prevention of stress, healthy food/healthy diet, unhealthy food/unhealthy diet, high-risk behavior, and self-care in the intervention group has increased significantly 2 months after intervention compared of control group (P < 0.001). Peer education increased knowledge and improved adolescents' health beliefs and behaviors. Therefore, training in adolescence in order to prevention of diabetes can be considered as an effective step, and the use of peer-led education in this field is recommended. Trial registration number IRCT20200811048361N1 from School of Public Health & Neuroscience Research Center-Shahid Beheshti University of Medical Sciences. Date applied: 30/12/2020. Date assigned: 01/12/2020.


Maturation and secretion of lipoprotein lipase in cultured adipose cells. I. Intracellular activation of the enzyme.
The intracellular pathway and the activation of lipoprotein lipase have been examined in differentiated Ob17 cells. These adipose cells were previously shown to secrete lipoprotein lipase during exposure to heparin. Treatment of the cells with cycloheximide and heparin leads to enzyme depletion, as shown by activity measurement and immunofluorescence microscopy. The repletion phase has been studied in the presence of monensin or carbonyl cyanide m-chlorophenylhydrazone, ionophores known to affect the intracellular transport of membrane and secretory proteins. Monensin-treated cells synthesize fully active lipoprotein lipase. Under these conditions the antigen accumulates in the Golgi apparatus and the heparin-stimulated enzyme release is extensively reduced. Carbonyl cyanide m-chlorophenylhydrazone-treated cells do not contain any enzyme activity but show detectable antigen which accumulates in the endoplasmic reticulum. Competition for binding to immobilized anti-lipoprotein lipase antibodies of mature and endoplasmic reticulum-sequestered antigens is observed. Carbonyl cyanide m-chlorophenylhydrazone removal is rapidly followed by a transient burst of enzyme activity and a redistribution of the antigen in the different subcellular compartments. Therefore, the results show that the activation of lipoprotein lipase is an intracellular event taking place after the enzyme exits from the endoplasmic reticulum and before it reaches the trans-Golgi cisternae.


Different levels of hyperoxia reversibly induce catalase activity in amphibian tadpoles.
Studies about the proposed antioxidant physiological role of the catalase (CAT) enzyme in relation to different environmental oxygen tensions are reported for the first time in amphibian larvae of Discoglossus pictus and Rana ridibunda perezi during their development. The CAT levels of whole tadpoles increased constantly in both species during the larval period, reaching a maximum during the metamorphic climax. All through development, CAT activity levels were always greater in D. pictus than in R. ridibunda perezi. This correlates well with the already reported higher SOD activity and hyperoxia resistance of the D. pictus species when compared to R. ridibunda perezi. Long-term acclimation to different levels of hyperoxia (40, 60, and 100% O2) showed dose-related increases in the CAT activity of D. pictus tadpoles. These increases did not take place when the animals were subjected to acute hyperoxia (24 h). The increase in CAT activity observed after 15 days of acclimation to acute hyperoxia (710 mm Hg: 100% O2) was reversed after 15 additional days of postacclimation to normal air (149 mm Hg O2). When recently metamorphosed frogs were acclimated to acute hyperoxia, significant increases in CAT activity were observed after 15 days, but not after 7 days. The results are interpreted as supporting a protective role for the CAT enzyme in amphibian larvae and froglets against oxygen toxicity.


Text message-based intervention, Keeping in Touch (KiT), to support youth as they transition to adult type 1 diabetes care: a protocol for a multisite randomised controlled superiority trial.
Transition from paediatric to adult care can be challenging for youth living with type 1 diabetes (T1D), as many youth feel unprepared to transfer to adult care and are at high risk for deterioration of glycaemic management and acute complications. Existing strategies to improve transition experience and outcomes are limited by cost, scalability, generalisability and youth engagement. Text messaging is an acceptable, accessible and cost-effective way of engaging youth. Together with adolescents and emerging adults and paediatric and adult T1D providers, we co-designed a text message-based intervention, Keeping in Touch (KiT), to deliver tailored transition support. Our primary objective is to test the effectiveness of KiT on diabetes self-efficacy in a randomised controlled trial. We will randomise 183 adolescents with T1D aged 17-18 years within 4 months of their final paediatric diabetes visit to the intervention or usual care. KiT will deliver tailored T1D transition support via text messages over 12 months based on a transition readiness assessment. The primary outcome, self-efficacy for diabetes self-management, will be measured 12 months after enrolment. Secondary outcomes, measured at 6 and 12 months, include transition readiness, perceived T1D-related stigma, time between final paediatric and first adult diabetes visits, haemoglobin A1c, and other glycaemia measures (for continuous glucose monitor users), diabetes-related hospitalisations and emergency department visits and the cost of implementing the intervention. The analysis will be intention-to-treat comparing diabetes self-efficacy at 12 months between groups. A process evaluation will be conducted to identify elements of the intervention and individual-level factors influencing implementation and outcomes. The study protocol version 7 July 2022 and accompanying documents were approved by Clinical Trials Ontario (Project ID: 3986) and the McGill University Health Centre (MP-37-2023-8823). Study findings will be presented at scientific conferences and in peer-reviewed publications. NCT05434754.


Incorporating Equity Concerns in Cost-Effectiveness Analyses: A Systematic Literature Review.
The aim of this study was to review analytical methods that enable the incorporation of equity concerns within economic evaluation. A systematic search of PubMed, Embase, and EconLit was undertaken from database inception to February 2021. The search was designed to identify methodological approaches currently employed to evaluate health-related equity impacts in economic evaluation studies of healthcare interventions. Studies were eligible if they described or elaborated on a formal quantitative method used to integrate equity concerns within economic evaluation studies. Cost-utility, cost-effectiveness, cost-benefit, cost-minimisation, and cost-consequence analyses, as well as health technology appraisals, budget impact analyses, and any relevant literature reviews were included. For each of the identified methods, we provided summaries of the scope of equity considerations covered, the methods employed and their key attributes, data requirements, outcomes, and strengths and weaknesses. A traffic light assessment of the practical suitability of each method was undertaken, alongside a worked example applying the different methods to evaluate the same decision problem. Finally, the review summarises the typical trade-offs arising in cost-effectiveness analyses and discusses the extent to which the evaluation methods are able to capture these. In total, 68 studies were included in the review. Methods could broadly be grouped into equity-based weighting (EBW) methods, extended cost-effectiveness analysis (ECEA), distributional cost-effectiveness analysis (DCEA), multi-criteria decision analysis (MCDA), and mathematical programming (MP). EBW and MP methods enable equity consideration through adjustment to incremental cost-effectiveness ratios, whereas equity considerations are represented through financial risk protection (FRP) outcomes in ECEA, social welfare functions (SWFs) in DCEA, and scoring/ranking systems in MCDA. The review identified potential concerns for EBW methods and MCDA with respect to data availability and for EBW methods and MP with respect to explicitly measuring changes in inequality. The only potential concern for ECEA related to the use of FRP metrics, which may not be relevant for all healthcare systems. In contrast, DCEA presented no significant concerns but relies on the use of SWFs, which may be unfamiliar to some audiences and requires societal preference elicitation. Consideration of typical cost-effectiveness and equity-related trade-offs highlighted the flexibility of most methods with respect to their ability to capture such trade-offs. Notable exceptions were trade-offs between quality of life and length of life, for which we found DCEA and ECEA unsuitable, and the assessment of lost opportunity costs, for which we found only DCEA and MP to be suitable. The worked example demonstrated that each method is designed with fundamentally different analytical objectives in mind. The review emphasises that some approaches are better suited to particular decision problems than others, that methods are subject to different practical requirements, and that significantly different conclusions can be observed depending on the choice of method and the assumptions made. Further, to fully operationalise these frameworks, there remains a need to develop consensus over the motivation for equity assessment, which should necessarily be informed with stakeholder involvement. Future research of this topic should be a priority, particularly within the context of equity evaluation in healthcare policy decisions.


The dialectical approach in group therapy.
A dialectical therapeutic approach has been used in treating individuals and families. Its application in group therapy is described with the aid of several anecdotal examples.


Paradigm shifts in malaria parasite biochemistry and anti-malarial chemotherapy.
A fatty acid synthesis (FAS) pathway was recently discovered and established in the obligate human parasite Plasmodium falciparum. Its inhibition by triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) leads to its classification as a type II FAS. Humans, the vertebrate host for the malarial parasite utilize type I FAS, which is not inhibited by triclosan. This discovery thus paves the way for novel approaches to the treatment of malaria. In direct contrast to the delayed-death phenotype associated with poisoning of the apicoplast using certain other drugs, the rapid and striking action of triclosan suggests the possibility of developing new drug(s) for the treatment of malaria.


Randomized controlled trial assessing two commercial weight loss programs in adults with overweight or obesity.
Lifestyle interventions remain the cornerstone for obesity treatment. Commercial programs offer one weight loss approach, yet the efficacy of few such programs have been rigorously investigated. The purpose of this study was to evaluate the efficacy of two commercial weight-loss programs, both utilizing pre-portioned meal replacements (MRs) and different levels of behavioural support, compared to a self-directed control diet in adults with overweight and obesity. In this 16-week study, participants were randomized to the low-calorie OPTAVIA® 5&1 Plan® with telephone coaching (OPT), the reduced-calorie Medifast® 4&2&1 self-guided plan (MED), or a self-directed, reduced-calorie control diet. Differences in weight, body composition (DXA) and body circumferences, all measured monthly, were assessed by analysis of covariance with sex and baseline measures as covariates. Of 198 participants randomized (80.8% female, BMI 34.2 kg/m2, 45.7 years), 92.3% completed the study. The OPT and MED groups had significantly greater reductions in body weight (-5.7% and - 5.0%, respectively, p < 0.0001), fat and abdominal fat mass (p < 0.0001) and waist and hip circumferences (p ≤ 0.003) than control at 16 weeks. Weight change was correlated with MR usage and completion of coaching support calls. Both structured commercial programs were more efficacious than a self-directed, reduced-calorie diet for weight loss and other anthropometric measures. Evidence-based commercial programs can be an important tool to help adults with overweight and obesity lose clinically relevant amounts of weight.