Fighting and Penalty Minutes Associated With Long-term Mortality Among National Hockey League Players, 1967 to 2022.
National Hockey League (NHL) players are exposed to frequent head trauma. The long-term consequences of repetitive brain injury, especially for players who frequently engage in fighting, remains unknown. To investigate the mortality rates and causes of death among NHL enforcers with more career fights and penalty minutes as compared with matched controls. This matched cohort study examined 6039 NHL players who participated in at least 1 game in the seasons between October 11, 1967, and April 29, 2022, using official NHL data. Cohorts designated as enforcer-fighter (E-F) and enforcer-penalties (E-P) were selected. The E-F cohort consisted of players who participated in 50 or more career fights (n = 331). The E-P cohort included players with 3 or more penalty minutes per game (n = 183). Control-matched NHL players were identified for each E-F player (control-fighter [C-F]) (n = 331) and each E-P player (control-penalties [C-P]) (n = 183). Fighting and penalty minutes were both used as proxies for head trauma exposure. Players with significantly increased exposure to fighting and penalties (E-F and E-P cohorts) were compared with NHL players with less frequent exposure to head trauma (C-F and C-P cohorts). Mortality rates and age at death of the enforcer and control cohorts, and their causes of death using data obtained from publicly available sources such as online and national news sources, including NHL.com. Among the 6039 NHL players identified (mean [SD] age, 47.1 [15.2] years), the mean (SD) number of fights was 9.7 (24.5). The mortality rates of E-F and C-F players (13 [3.9%] vs 14 [4.2%], respectively; P = .84) or E-P and C-P players (13 [7.1.%] vs 10 [5.5%]; P = .34) were not significantly different. The mean (SD) age at death was 10 years younger for E-F players (47.5 [13.8] years) and E-P players (45.2 [10.5] years) compared with C-F players (57.5 [7.1] years) and C-P players (55.2 [8.4] years). There was a difference in causes of death between the control and enforcer players (2 neurodegenerative disorders, 2 drug overdoses, 3 suicides, and 4 vehicular crashes among enforcers vs 1 motor vehicle crash among controls; P = .03), with enforcers dying at higher rates of overdose (2 of 21 [9.5%] vs 0 of 24) and suicide (3 of 21 [14.3%] vs 0 of 24) (P = .02). The findings of this matched cohort study indicate that there is no difference in overall mortality rates between NHL enforcers and controls. However, being an enforcer was associated with dying approximately 10 years earlier and more frequently of suicide and drug overdose.


Radiation and Second Primary Thyroid Cancer Following Index Head and Neck Cancer.
Radiation is thought to increase risk of developing second primary thyroid cancer (SPTC). This study estimated the rate of SPTC following index head and neck cancer (HNC) and determined whether radiation treatment among HNC survivors increased SPTC risk. Retrospective data analysis. The Surveillance, Epidemiology, and End Results database (1975-2014) was queried for cases of index HNC (N = 127,563) that developed SPTC. Adjusted multivariable competing risk proportional hazards model tested risk of developing a SPTC following index HNC. Sensitivity analyses using proportional hazards models were also performed restricting data to patients who 1) received both radiation and chemotherapy and 2) radiation alone. Only 0.2% of index HNC survivors (n = 229) developed SPTC, yielding a rate of 26.1 per 100,000 person-years. For every increasing year of age at diagnosis, patients were 3% less likely to develop an SPTC (adjusted hazard ratio [aHR] = 0.97, 95% CI: 0.96-0.98). Males were also less likely to develop an SPTC (aHR = 0.73, 95% CI: 0.55-0.96). Radiation (aHR = 0.92, 95% CI: 0.68-1.25), surgery (aHR = 0.79, 95% CI: 0.56-1.11), and chemotherapy (aHR = 1.13, 95% CI: 0.76-1.69) were not significantly associated with developing SPTC. The sensitivity models also did not find an association between treatment and risk of SPTC. Rate of developing SPTC following index HNC was very low, and previous exposure to radiation did not significantly increase risk in our study population. More studies are needed to understand the increasing incidence of thyroid cancer across the United States. NA Laryngoscope, 129:1014-1020, 2019.


Falsely elevated urinary excretion of catecholamines and metanephrines in patients receiving labetalol therapy.
Five patients with essential hypertension who were receiving treatment with the beta- and alpha-adrenoreceptor-blocking drug labetalol had elevated urinary excretion of catecholamines. When measured with a radioenzymatic assay, all five subjects had elevated urinary excretion of norepinephrine and normal urinary excretion of epinephrine; when measured with a fluorometric assay, four subjects had elevated urinary excretion of epinephrine with normal urinary excretion of norepinephrine, and one subject had elevated urinary norepinephrine excretion with normal urinary excretion of epinephrine. In three subjects who could be reevaluated three days to two months after labetalol therapy was discontinued, the urinary catecholamine levels had returned toward normal. Our studies indicate that labetalol produced a false elevation of urinary catecholamine levels. Although labetalol also interfered with the measurement of urinary excretion of metanephrine, it did not interfere with the measurement of urinary excretion of vanillylmandelic acid, homovanillic acid, 5-hydroxyindoleacetic acid, and serotonin, and it probably did not interfere with the measurement of plasma concentrations of dopamine, norepinephrine, and epinephrine. We conclude that labetalol therapy should be discontinued, and another beta-blocking drug, such as propranolol, that does not interfere with these tests should be temporarily substituted at least three days before a patient collects a 24-hour urine for measurement of the urinary excretion of catecholamines and metanephrine.


Development of a novel animal model of rotator cuff tear arthropathy replicating clinical features of progressive osteoarthritis with subchondral bone collapse.
To establish an animal model of modified cuff tear arthropathy (mCTA) in order to better replicate the pathophysiology associated with rotator cuff tear-induced humeral head collapse. mCTA was induced by transection of the rotator cuff, the long head of the biceps brachii (LHB), and superior half of the joint capsule in the right shoulder of 12-week-old rats; the left shoulder underwent sham surgery. The severity of CTA was quantitated using the Murine Shoulder Arthritis Score (MSAS). The trabecular bone of the humeral head and metaphysis was analyzed using bone histomorphometry. The expression of proinflammatory cytokines and catabolic enzymes was evaluated immunohistochemically. In the mCTA model, the MSAS increased starting from 2 weeks after induction, and there was notable subchondral bone collapse with fibrous cells at 4 weeks. The mCTA cartilage exhibited positive staining for TNF-α, IL-1β/6, MMP-3/13, and ADAMTS5. The trabecular bone volume was reduced not only in the subchondral bone but also in the metaphysis of the humeri, and bone resorption was enhanced in these areas. In the collapsed subchondral bone, both bone formation and resorption were increased. The fibrous cells showed expression of TNF-α, IL-6, and MMP-13, along with specific markers of mesenchymal stem cells. Furthermore, the fibrous cells showed osteoblastic characteristics (RUNX2-positive) and expressed RANKL. The LHB and the capsuloligamentous complex are critical stabilizers of the glenohumeral joint, serving to prevent the advancement of CTA following massive rotator cuff tears. Fibrous cells appear to play a role in the humeral head bone resorption.


Periosteal chondrosarcoma: an unusual juxtacortical sarcoma.
Periosteal chondrosarcoma is a rare tumor. It can be difficult to diagnose radiographically and pathologically and can be confused with periosteal osteosarcoma; however, the treatment of these two lesions is quite different. Increased awareness of imaging features of this lesion, particularly those that can help differentiate it from other surface-based tumors, can help one recognize this entity. We report the case of a periosteal chondrosarcoma in a young woman, highlighting the diagnostic imaging features of this disease, and her treatment with a joint-sparing geometric resection of the distal femur, using patient-specific 3D-printed cutting guides and matched allograft reconstruction.


Enzymatic semisynthesis of human insulin: an update.
Peptide bond formation can be enzymatically catalysed by the reverse reaction of proteases. Application is seen in the industrial production of human insulin. Human insulin derivative can be enzymatically prepared using either porcine insulin or the single chain B(1-29)-A(1-21) insulin precursor as the starting material. This is accomplished by either (1) digesting the starting material at Lys29 with Achromobacter lyticus protease I (Ach) and then coupling with Thr-X (X = blocking residue) (two-step reaction) or (2) subjecting Ala-B30 of porcine insulin or Gly-A1 of the single chain insulin precursor to transpeptidation with Thr-X (one-step reaction). Trypsin and Ach can be used for either type of reaction and, in the immobilized form, for the two-step reaction. Since the single chain insulin precursor can be produced by gene technology (yeast), use of immobilized trypsin or Ach and the two-step reaction using the single chain insulin precursor as the starting material ensures the continuous production of human insulin making it a feasible method for industrial manufacture.


Applying formalized rules for treatment procedures to data delivered by personal medical devices.
The paper presents a novel approach to online application of formalized rules for medical treatment procedures when processing data from personal medical devices. The rules are formalized by using a rule-based reasoning approach and are applied in order to enhance patient safety and support physicians in their daily work. The presented approach relies on dividing data processing into two stages: (1) the event processing stage and (2) the knowledge application stage. At the event processing stage raw data produced by personal medical devices is transformed into an aggregated/correlated form, as required by the rules for treatment procedures. At the knowledge application stage formalized rules are applied to transformed data, resulting in execution of various support actions. This paper describes how rules for treatment of patients suffering from cardiovascular diseases can be expressed in terms of an event processing statement set and a rule engine knowledge base. The technical feasibility of the proposed approach is supported by a detailed description of the TeleCARE remote healthcare framework - an implementation of the proposed approach along with evaluation performed using a large number of simulated personal medical devices.


Hyperfibrotic myelodysplastic syndrome: a report of three cases from north India.
Extensive fibrosis in myelodysplastic syndromes (MDS) is distinctly infrequent. Herein, we report three rare cases of hyperfibrotic MDS. This entity should be classified separately in the chronic myeloproliferative disease (CMPD)-MDS group due to variable clinical presentation and poor prognosis.


"Residential greenness and site-specific cancer: A registry based cohort of 144,427 participants with a 21-years of follow-up, Tel-Aviv district, Israel".
Few longitudinal studies evaluated the beneficial associations between cumulative residential greenness and site-specific cancer. Our objective was to evaluate the associations between cumulative residential greenness exposure and site-specific cancer incidence (lung, bladder, breast, prostate, and skin cancer) within a registry-based cohort study. This study was based on 144,427 participants who lived in the Tel Aviv district during 1995-2015. The residential greenness exposure was estimated for every participant, as the weighted mean residential greenness exposure, based on the mean Normalized Difference Vegetation Index (NDVI) in the residential area and the duration of the residence in this area. Cox regression models were used to evaluate the unadjusted and adjusted associations between exposure to greenness and cancer incidence during 1998-2015 (Hazard Ratios (HRs) and 95% Confidence Intervals (CIs)). Covariates included in adjusted models were selected based on prior knowledge and directed acyclic graphs. We imputed missing data and further sensitivity analyses were conducted. After adjustments, beneficial associations between exposure to greenness and cancer incidence were observed. An interquartile range (IQR) increase in NDVI was associated with a lower HRs for lung cancer (HRadj. = 0.75 95% CI: 0.66-0.85), bladder cancer (HRadj. = 0.71, 95% CI: 0.62-0.82), breast cancer (HRadj. = 0.81, 95% CI: 0.74-0.88), prostate cancer (HRadj. = 0.77, 95% CI: 0.70-0.86) and skin cancer (HRadj. = 0.78, 95% CI: 0.69-0.88). Generally, the patterns of associations were consistent between complete-case models and imputed models, when estimated for participants aged 16 years or 40 years and older at baseline, when stratified by area level socioeconomic status, when evaluated for non-movers participants and after further adjustment to social determinants of health. Residential greenness may reduce the risk for lung, bladder, breast, prostate, and skin cancers. If our observations will be replicated, it may present a useful avenue for public-health intervention to reduce cancer burden.


Dietary resistant starch increases hypothalamic POMC expression in rats.
Resistant starch (RS) is fermentable dietary fiber. Inclusion of RS in the diet causes decreased body fat accumulation and altered gut hormone profile. This study investigates the effect of feeding RS on the neuropeptide messenger RNA (mRNA) expressions in the arcuate nucleus (ARC) of the hypothalamus and whether vagal afferent nerves are involved. The rats were injected intraperitoneally with capsaicin to destroy unmyelinated small vagal afferent nerve fibers. The cholecystokinin (CCK) food suppression test was performed to validate the effectiveness of the capsaicin treatment. Then, capsaicin-treated rats and vehicle-treated rats were subdivided into a control diet or a RS diet group, and fed the corresponding diet for 65 days. At the end of study, body fat, food intake, plasma peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), and hypothalamic pro-opiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AgRP) gene expressions were measured. RS-fed rats had decreased body fat, increased POMC expression in the hypothalamic ARC, and elevated plasma PYY and GLP-1 in both the capsaicin and vehicle-treated rats. Hypothalamic NPY and AgRP gene expressions were not changed by RS or capsaicin. Therefore, destruction of the capsaicin-sensitive afferent nerves did not alter the response to RS in rats. These findings suggest that dietary RS might reduce body fat through increasing the hypothalamic POMC expression and vagal afferent nerves are not involved in this process. This is the first study to show that dietary RS can alter hypothalamic POMC expression.


Integrated source-free all optical sampling with a sampling rate of up to three times the RF bandwidth of silicon photonic MZM.
Source-free all optical sampling, based on the convolution of the signal spectrum with a frequency comb in an electronic-photonic, co-integrated silicon device will be presented for the first time, to the best of our knowledge. The method has the potential to achieve very high precision, requires only low power and can be fully tunable in the electrical domain. Sampling rates of three and four times the RF bandwidths of the photonics and electronics can be achieved. Thus, the presented method might lead to low-footprint, fully-integrated, precise, electrically tunable, photonic ADCs with very high-analog bandwidths for the digital infrastructure of tomorrow.


Data on the gene expression of cardiomyocyte exposed to hypothermia.
Hypothermia is widely used in neurosurgery and cardiac surgeries. However, little is known about the underlying molecular mechanisms. We previously reported that the transcriptome responses of cardiomyocyte exposed to hypothermia, "The transcriptome responses of cardiomyocyte exposed to hypothermia" [4]. Herein, we provide the hypothermia inhibited proliferation of cardiomyocyte cells in vitro and the details of transcription factors in regulation of differentially expressed genes.


Microbial detection in microfluidic devices through dual staining of quantum dots-labeled immunoassay and RNA hybridization.
This paper reported the development of a microfludic device for the rapid detection of viable and nonviable microbial cells through dual labeling by fluorescent in situ hybridization (FISH) and quantum dots (QDs)-labeled immunofluorescent assay (IFA). The coin sized device consists of a microchannel and filtering pillars (gap=1-2 microm) and was demonstrated to effectively trap and concentrate microbial cells (i.e. Giardia lamblia). After sample injection, FISH probe solution and QDs-labeled antibody solution were sequentially pumped into the device to accelerate the fluorescent labeling reactions at optimized flow rates (i.e. 1 and 20 microL/min, respectively). After 2 min washing for each assay, the whole process could be finished within 30 min, with minimum consumption of labeling reagents and superior fluorescent signal intensity. The choice of QDs 525 for IFA resulted in bright and stable fluorescent signal, with minimum interference with the Cy3 signal from FISH detection.


Blocking carbohydrate absorption and weight loss: a clinical trial using Phase 2 brand proprietary fractionated white bean extract.
Phase 2' starch neutralizer brand bean extract product ("Phase 2") is a water-extract of a common white bean (Phaseolus vulgaris) that has been shown in vitro to inhibit the digestive enzyme alpha-amylase. Inhibiting this enzyme may prevent the digestion of complex carbohydrates, thus decreasing the number of carbohydrate calories absorbed and potentially promoting weight loss. Fifty obese adults were screened to participate in a randomized, double-blind, placebo-controlled study evaluating the effects of treatment with Phase 2 versus placebo on weight loss. Participants were randomized to receive either 1500 mg Phase 2 or an identical placebo twice daily with meals. The active study period was eight weeks. Thirty-nine subjects completed the initial screening process and 27 subjects completed the study. The results after eight weeks demonstrated the Phase 2 group lost an average of 3.79 lbs (average of 0.47 lb per week) compared with the placebo group, which lost an average of 1.65 lbs (average of 0.21 lb per week), representing a difference of 129 percent (p=0.35). Triglyceride levels in the Phase 2 group were reduced an average of 26.3 mg/dL, more than three times greater a reduction than observed in the placebo group (8.2 mg/dL) (p=0.07). No adverse events during the study were attributed to the study medication. Clinical trends were identified for weight loss and a decrease in triglycerides, although statistical significance was not reached. Phase 2 shows potential promise as an adjunct therapy in the treatment of obesity and hypertriglyceridemia and further studies with larger numbers of subjects are warranted to conclusively demonstrate effectiveness.


Words of wisdom. Re: Carbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapy. Stillebroer AB, Mulders PFA, Boerman DC, Oyen WJG, Oosterwijk. E Eur Urol. In press. DOI: 10.1016/j.eururo.2010.03.015.
The authors analysed the potential use and limitations of carbonic anhydrase IX (CAIX) antigen as a marker with diagnostic and prognostic value in cases of clear-cell renal cell carcinoma (ccRCC). The study reports that >95% of ccRCCs show high and homogeneous levels of CAIX expression by reverse transcription-polymerase chain reaction and immunohistochemistry. Monoclonal antibody (MAb) G250 has a high affinity for the CAIX antigen. Using MAb G250 in iodine 131-G250 radioimmunoscintigraphy (RIS) and fluorodeoxyglucose F 18 positron emission tomography (PET) can detect primary ccRCC and metastatic sites through the affinity with CAIX antigen. CAIX expression in ccRCC is also presented as a significant and independent adverse predictor of survival. Finally, CAIX has a potential role as a predictor of response to immunotherapy. Seventy-eight percent of renal cell carcinomas(RCCs) responding to interleukin-2 therapy showed high CAIX-expressing primary tumours. Similarly, CAIX expression was associated with a significantly higher treatment response rate in patients with metastatic RCC who received sorafenib.


Quantitative assessment of effects of phase aberration and noise on high-frame-rate imaging.
The goal of this paper is to quantitatively study effects of phase aberration and noise on high-frame-rate (HFR) imaging using a set of traditional and new parameters. These parameters include the traditional -6-dB lateral resolution, and new parameters called the energy ratio (ER) and the sidelobe ratio (SR). ER is the ratio between the total energy of sidelobe and the total energy of mainlobe of a point spread function (PSF) of an imaging system. SR is the ratio between the peak value of the sidelobe and the peak value of the mainlobe of the PSF. In the paper, both simulation and experiment are conducted for a quantitative assessment and comparison of the effects of phase aberration and noise on the HFR and the conventional delay-and-sum (D&S) imaging methods with the set of parameters. In the HFR imaging method, steered plane waves (SPWs) and limited-diffraction beams (LDBs) are used in transmission, and received signals are processed with the Fast Fourier Transform to reconstruct images. In the D&S imaging method, beams focused at a fixed depth are used in transmission and dynamically focused beams are used in reception for image reconstruction. The simulation results show that the average differences between the -6-dB lateral beam widths of the HFR imaging and the D&S imaging methods are -0.1337mm for SPW and -0.1481mm for LDB, which means that the HFR imaging method has a higher lateral image resolution than the D&S imaging method since the values are negative. In experiments, the average differences are also negative, i.e., -0.2804mm for SPW and -0.3365mm for LDB. The results for the changes of ER and SR between the HFR and the D&S imaging methods have negative values, too. After introducing phase aberration and noise, both simulations and experiments show that the HFR imaging method has also less change in the -6-dB lateral resolution, ER, and SR as compared to the conventional D&S imaging method. This means that the HFR imaging method is less sensitive to the phase aberration and noise. Based on the study of the new parameters on the HFR and the D&S imaging methods, it is expected that the new parameters can also be applied to assess quality of other imaging methods.


Differential effects of estrogen in the injured forebrain of young adult and reproductive senescent animals.
Estrogen attenuates neural damage resulting from a variety of experimental injury models in adult female rats. To determine whether estrogens neuroprotective actions are age-specific, the present study compared the effects of estrogen on young adult and reproductive senescent animals subject to excitotoxic injury to the forebrain. NMDA was injected bilaterally into the olfactory bulbs of estrogen and placebo-replaced young adult and reproductive senescent animals. Lysates of the olfactory bulb and its basal forebrain afferent, the horizontal limb of the diagonal band of Broca (hlDBB), harvested 24h later were analyzed for expression of IL-1beta, IL-10, and nerve growth factor (NGF). NMDA injections resulted in local activation of microglia and an increase in IL-1beta. Estrogen replacement decreased IL-1beta expression in young adult females, but paradoxically enhanced its expression in reproductive senescent females. Furthermore, bulb injury increased IL-1beta production in the hlDBB of reproductive senescent animals although estrogen replacement was able to suppress lesion-induced expression of this cytokine. In both, the olfactory bulb and hlDBB, constitutive expression of the anti-inflammatory cytokine IL-10 was significantly higher while that of NGF was almost 50% lower in senescent animals as compared to young adults, indicating that aging preferentially altered Th2-type secretions. The present findings are consistent with our earlier observations that estrogen does not exert trophic effects in the aging forebrain and supports the hypothesis that estrogen treatment to reproductive senescent females may exacerbate neural injury.


60-kDa Tat-interactive protein (TIP60) positively regulates Th-inducing POK (ThPOK)-mediated repression of eomesodermin in human CD4+ T cells.
The abundant expression of IFNγ in Th-inducing POK (ThPOK)-deficient CD4(+) T cells requires the activation of Eomesodermin (Eomes); however, the underlying mechanism of this phenomenon remains unclear. Here we report that ThPOK binds directly to the promoter region of the Eomes gene to repress its expression in CD4(+) T cells. We identified the histone acetyltransferase TIP60 as a co-repressor of ThPOK-target genes, where ectopically expressed TIP60 increased ThPOK protein stability by promoting its acetylation at its Lys(360) residue to then augment the transcriptional repression of Eomes. Moreover, knockdown of endogenous TIP60 abolished the stabilization of ThPOK in CD4(+) T cells, which led to the transcriptional activation of Eomes and increased production of IFNγ. Our results reveal a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNγ production, which could contribute to the regulation of inflammation.


Reactivation of Behçet's disease in the course of multicentric HHV8-positive Castleman's disease: long-term complete remission by a combined chemo/radiation and interferon-alpha therapy regimen.
We used a new combined chemo- (COP/ABVD), radiation and interferon-alpha (10 x 10(6) IU s.c. 3x per week/12 months) therapy regimen to treat severe multicentric Castleman's disease (CD) complicated by relapsing Behcet's disease (BD) manifestations. More than 16 years after diagnosis of CD the patient remains in very good clinical condition, with remission of all CD and BD manifestations 13 months after discontinuation of the interferon-alpha treatment. In addition, our clinicopathological, immunohistological and virological data suggest a pathogenetic link between CD and BD via activation of pre-existing BD-specific plasma cells due to CD-related HHV8-induced overexpression of interleukin-6.


Principles and equations for measuring and interpreting protein stability: From monomer to tetramer.
The ability to measure the thermodynamic stability of proteins with precision is important for both academic and applied research. Such measurements rely on mathematical models of the protein denaturation profile, i.e. the relation between a global protein signal, corresponding to the folding states in equilibrium, and the variable value of a denaturing agent, either heat or a chemical molecule, e.g. urea or guanidinium hydrochloride. In turn, such models rely on a handful of physical laws: the laws of mass action and conservation, the law that relates the protein signal and concentration, and the one that relates stability and denaturant value. So far, equations have been derived mainly for the denaturation profiles of homomeric proteins. Here, we review the underlying basic physical laws and show in detail how to derive model equations for the unfolding equilibria of homomeric or heteromeric proteins up to trimers and potentially tetramers, with or without folding intermediates, and give full demonstrations. We show that such equations cannot be derived for pentamers or higher oligomers except in special degenerate cases. We expand the method to signals that do not correspond to extensive protein properties. We review and expand methods for uncovering hidden intermediates of unfolding. Finally, we review methods for comparing and interpreting the thermodynamic parameters that derive from stability measurements for cognate wild-type and mutant proteins. This work should provide a robust theoretical basis for measuring the stability of complex proteins.


Ferric perchlorate hydrate as a new catalyst for highly efficient esterification of cellulose at room temperature.
Ferric perchlorate was tested for the first time as a new catalyst to accelerate the esterification of microcrystalline cellulose (MCC) at room temperature in a less amount of acetic anhydride compared to the amount used in the conventional methods. It was possible to manufacture cellulose acetate (CA) with a high yield of up to 94%. The influence of changes in reaction time, catalyst amounts, and acetic anhydride on the characterization of cellulose acetate produced was investigated. The optimum condition for esterification of 2.0 g (12.34 mmol) MCC was found to be: 10 mL (105.98 mmol) AC2O, 200 mg (0.564 mmol, anhydrous basis) of Fe(ClO4)3·xH2O and 1 h reaction time at room temperature. The substitution degree of CA was investigated by FTIR and 1H-NMR spectroscopy. Thermal stability of CA was studied using TGA, DTA and DSC analyses. The degree of polymerization and the polydispersity index (PDI) were obtained using Gel permeation chromatography (GPC). This study verified the direct and efficient synthesis of di- and tri-cellulose acetate in one-pot reaction using Fe(ClO4)3·xH2O as a catalyst without using solvent.


Use of embryo transfer to alleviate infertility caused by heat stress.
Heat stress (HS) has a pronounced deleterious effect on fertility in dairy herds throughout the world, especially in hot and humid summer months in tropical and subtropical areas. Summer HS reduces feed intake and increases negative energy balance, induces changes in ovarian follicular dynamics, reduces estrus detection rates and alters oviductal function leading to fertilization failure and early embryonic death. Furthermore, oocytes harvested from lactating cows during summer HS have a decreased ability to develop to the blastocyst stage after in vitro fertilization when compared with oocytes harvested during winter. The present manuscript describes the detrimental effect of HS on reproduction, with emphasis on preovulatory oocytes and carry over effects of HS on embryo development and P/AI. Embryo transfer (ET) has been an effective tool to reestablish fertility during HS because it bypasses the damage to the oocyte and early embryo caused by hyperthermia. Therefore, a management strategy to maintain increased fertility throughout the year would be to produce embryos during the cooler months, when oocyte quality is greater, and use them to produce pregnancies during the periods of HS, when oocyte quality is compromised. However, this strategy only can be implemented using cryopreserved embryos, what is still limiting. During the warmer months, the use of heifers or non-lactating cows as oocyte or embryo donors may facilitate embryo production, mainly because of the lesser deleterious effects of HS comparing to lactating cows. Also, genetic selection of donors for thermoregulation ability is one potential strategy to mitigate effects of HS and increase embryo production during the warmer months. These alternatives enable the transference of fresh embryos with more efficiency during HS periods. Additionally, the application of timed ET protocols, which avoid the need for estrus detection in recipients, has facilitated management and improved the efficiency of ET programs during HS.


Exchange and interactions between lipid layers at the surface of a liposome solution.
Lipid organization and lipid transport processes occurring at the air-water interface of a liposome (lipid vesicle) solution are studied by conventional surface pressure-area measurements and interpreted by an adequate theory. At the interface of a dioleoyl phosphatidylcholine vesicle solution, used for demonstration, a well defined two layer structure selfassembles: vesicles disintegrate at the interface forming a surface-adsorbed lipid monolayer, which prevents further disintegration beyond about 1 dyne/cm surface pressure. A layer of vesicles now assembles in close association with the monolayer. This layer is in vesicle diffusion exchange with the solution and in lipid exchange with the monolayer. The lipid exchange occurs exclusively between the monolayer and the outer lipid layer of the vesicles; it is absent between outer and inner vesicle layers. Equilibration of the lipid density in the monolayer with that in the vesicle outer layer provides a coherent and quantitative explanation of the observed hysteresis effects and equilibrium states. The correspondence between monolayer and vesicle outer layer is traced down to equilibrium constants and rate constants and their dependences on surface pressure, vesicle size and concentration. Other alternate realizations of surface structure and exchange, including induced lipid flip-flop within vesicles or vesicle monolayer adhesion or fusion are potential applications of the proposed analysis.


From biomolecules to biogeochemistry: Exploring the interaction of an indigenous bacterium with gold.
Specialised microbial communities colonise the surface of gold particles in soils/sediments, and catalyse gold dissolution and re-precipitation, thereby contributing to the environmental mobility and toxicity of this 'inert' precious metal. We assessed the proteomic and physiological response of Serratia proteamaculans, the first metabolically active bacterium enriched and isolated directly from natural gold particles, when exposed to toxic levels of soluble Au3+ (10 μM). The results were compared to a metal-free blank, and to cultures exposed to similarly toxic levels of soluble Cu2+ (0.1 mM); Cu was chosen for comparison because it is closely associated with Au in nature due to similar geochemical properties. A total of 273 proteins were detected from the cells that experienced the oxidative effects of soluble Au, of which 139 (51%) were upregulated with either sole expression (31%) or had synthesis levels greater than the Au-free control (20%). The majority (54%) of upregulated proteins were functionally different from up-regulated proteins in the bacteria-copper treatment. These proteins were related to broad functions involving metabolism and biogenesis, followed by cellular process and signalling, indicating significant specificity for Au. This proteomic study revealed that the bacterium upregulates the synthesis of various proteins related to oxidative stress response (e.g., Monothiol-Glutaredoxin, Thiol Peroxidase, etc.) and cellular damage repair, which leads to the formation of metallic gold nanoparticles less toxic than ionic gold. Therefore, indigenous bacteria may mediate the toxicity of Au through two different yet simultaneous processes: i) repairing cellular components by replenishing damaged proteins and ii) neutralising reactive oxygen species (ROS) by up-regulating the synthesis of antioxidants. By connecting the fields of molecular bacteriology and environmental biogeochemistry, this study is the first step towards the development of biotechnologies based on indigenous bacteria applied to gold bio-recovery and bioremediation of contaminated environments.


Absence of antibodies to human herpesvirus-6 in patients with slowly-progressive human immunodeficiency virus type 1 infection.
To evaluate a possible role for Human Herpesvirus-type 6 (HHV-6) coinfection as a co-factor in the progression of HIV-1 disease, we investigated the prevalence of seropositivity for HHV-6 in a cohort of HIV-1 infected patients. These patients were retrospectively divided into two groups according to the decline of CD4+ T cells during the follow up: 11 were classified as rapid decliners (less than 400 CD4+/cmm within 1 year), and 38 as slow decliners (greater than 400 CD4+/cmm after at least 4 years' follow up). HHV-6 antibodies were detected by a commercial immunofluorescence assay and by a Western blotting assay developed in our laboratory. Our results show that Western blot appears to provide results satisfactorily free of false positivities. We found that the frequency of HHV-6 seropositivity was significantly lower in the group of slow decliners, compared both to rapid decliners and to the general population. These data suggest a role for HHV-6 co-infection in the progression of HIV-1 disease.


Risk factors for development of incipient and overt diabetic nephropathy in type 1 diabetic patients: a 10-year prospective observational study.
To evaluate prospectively putative risk factors for development of microalbuminuria and macroalbuminuria in type 1 diabetes. Prospective observational study of a cohort of type 1 diabetic patients followed in the outpatient clinic at Steno Diabetes Center for < or =10 years (median 9 years). We followed 537 patients aged > or =18 years with type 1 diabetes, with duration of diabetes > or =5 years, with normoalbuminuria (urinary albumin excretion rate < or =30 mg/24 h), and who were not taking antihypertensive medication. Risk factors for development of microalbuminuria and macroalbuminuria were evaluated. The mean progression of urinary albumin excretion rate was 7.6% (SE 0.8) per year. During follow-up, 134 patients (25%) progressed to persistent microalbuminuria or macroalbuminuria (>30 mg/24 h in two of three consecutive urine samples). Cox multiple regression analysis using baseline values of putative predictors of progression showed the following significant predictors of progression from normoalbuminuria to microalbuminuria or macroalbuminuria: baseline log urinary albumin excretion rate 2.63 (relative risk; 95% CI 1.65-4.19), HbA(1c) 1.13% (1.04-1.23), presence of any retinopathy 1.90 (1.26-2.88), and smoking 1.61 (1.11-2.33). Sex, duration of diabetes, arterial blood pressure, serum creatinine, height, and social class were not risk factors. Our study suggests that several potentially modifiable risk factors predict the development of microalbuminuria and macroalbuminuria in type 1 diabetic patients.


Ubiquitin-Conjugating Enzyme E2 L3 is Downregulated by the Chikungunya Virus nsP2 Protease.
Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus that causes chikungunya fever in humans. The CHIKV non-structural protein 2 (nsP2) is a multifunctional protein that additionally modulates the host cell to dampen the innate immune response and inhibit other cellular processes. To further investigate the interactions of nsP2 with host cells, the protease domain of CHIKV nsP2 (nsP2-pro) is transfected into Hela cells, and differential protein expression is detected by 2D polyacrylamide gel electrophoresis. A total of 21 differentially regulated (six upregulated, 15 downregulated) spots are observed, of which five are identified by mass spectrometry. The downregulation of one of the identified proteins, ubiquitin-conjugating enzyme E2 L3 (UBE2L3) is confirmed by western blotting of both nsP2-pro transfection and CHIKV natural infection, and the downregulation of UBE2L3 is additionally shown to require an enzymatically active nsP2 protease domain. Transfection of full length UBE2L3 into HEK293T/17 cells prior to CHIKV infection reduce levels of infection and E protein expression but do not alter RNA genome levels. These results suggest that UBE2L3 is a cellular target of the CHIKV nsP2 protease, and this possibly mediates the pathogenesis of chikungunya fever.


Prognostic value of concentration of pregnancy-specific beta 1-glycoprotein (SP1) in serum of patients with breast cancer.
Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by particle counting immunoassay in serum from 46 healthy female blood donors, 33 patients with benign mastopathy and 84 patients with breast cancer before operation and during follow-up. Values greater than 1 micrograms/1 were found more frequently with benign mastopathies (11/33) and in patients with breast cancer at stage 2 (20/48), 3 (4/9), and 4 (7/10) than in healthy female blood donors (3/46). The survival rate after 4 years was significantly lower in patients with SP1 level greater than 1 microgram/1 before tumor resection (52% vs. 87%). The difference remained significant when only patients in stage 2 were taken into account (57% vs. 85%). A highly significant (r = 0.64; N = 46) negative correlation was observed between the concentration of SP1 in serum and the concentration of estrogen receptor in the tumor. The longitudinal study of patients in stage 2 indicated that, of the 15 whose SP1 concentration fell below 1 microgram/1 after operation, 14 survived over 4 years whereas during the same period, 9 of the 10 patients whose SP1 value remained higher than 1 microgram/1 died.


Managing dermatology patients who prefer "all natural" treatments.
Dermatology patients are expressing a growing interest in complementary and alternative medicine (CAM) and natural treatment options for management of dermatologic conditions. Counseling on the optimal integration of CAM with conventional therapeutic approaches can be daunting for practitioners who do not feel well-versed in these modalities. A productive conversation between the clinician and patient seeking natural treatments should address the appropriate role and scope of CAM in a therapeutic plan, which is best suited for use as maintenance therapy or to augment traditional pharmaceutical or procedural interventions. Understanding the patient's goals, discussing evidence-based conventional and complementary treatment options, and employing shared decision making can enhance the clinical encounter and strengthen the physician-patient relationship.


Soil algae as a potential carrier for nanoplastics: Adsorption and internalization of nanoplastics in algal cells.
Although plastics are widely distributed in soil environments, few studies have assessed their effects on different test species. In this study, the responses (adsorption or internalization) of two green algal species (Chlorococcum infusionum and Chlamydomonas reinhardtii) to nanoplastics in soil were evaluated via microscopic analysis for nine weeks; additionally, the effects of polystyrene (PS) nanoplastics on their photosynthetic activity and growth were assessed. The results showed that PS nanoplastics and C. infusionum or C. reinhardtii cells were aggregated with the formation of palmelloid colonies; additionally, internalization of PS nanoplastics to C. reinhardtii cells was verified. However, no significant effects of PS nanoplastics on photosynthetic activity and growth of soil algae were observed. Algae were more likely to be threatened by plastic aggregation in the soil environment than in the aquatic environment due to the formation of a mucilaginous sheath on their cell. Our results highlighted that soil algae are a potential carrier of nanoplastics to other organisms in the food chain due to plastic aggregation through adsorption or internalization. This study will enhance our understanding of nanoplastic distribution in soil algae.


Development of a comprehensive understanding of aggregation-settling movement of CeO2 nanoparticles in natural waters.
Parameters such as the settling rate, aggregation rate, and collision frequency in predictive models used to describe the fate of nanoparticles (NPs) are very important for the risk assessment of NPs in the environment. In this study, CeO2 NPs were chosen as the model particles to investigate such parameters through aggregation-settling experiments under environmentally relevant conditions. The results indicate that natural colloids (Ncs) have no effect on the settling of NPs in seawaters, whereas they stabilize the NPs at a low initial particle concentration and promote the heteroaggregation of NPs at a high initial particle concentration in lake waters. In all cases, a suspended sediment absorbs the NPs and Ncs as mixed aggregates, resulting in a rapid settling. Furthermore, the calculation results of the model indicate that the shear force increases the collision frequency of the NPs by 4-5 orders of magnitude higher than that in quiescent waters. However, the break-up effect by the shear force is more obvious, namely, the shear force hinders the aggregation of NPs in natural waters, instead of promoting aggregation. Remarkably, a negative value of the dis-heteroaggregation rate based on the combined von Smoluchowski-Stokes equation can reflect the hindering effect on the aggregation process. The results of this study will provide scientific and accurate guidance for the parameter selection in the existing prediction model and contribute to a prediction of the fate and transport of NPs in the environment.


H5N1 receptor specificity as a factor in pandemic risk.
The high pathogenicity of H5N1 viruses in sporadic infections of humans has raised concerns for its potential to acquire the ability to transmit between humans and emerge as a highly pathogenic pandemic virus. Because avian and human influenza viruses differ in their specificity for recognition of their host cell receptors, receptor specificity represents one barrier for efficient transmission of avian viruses in human hosts. Over the last century, each influenza virus pandemic has coincided with the emergence of virus with an immunologically distinct hemagglutinin exhibiting a 'human-type' receptor specificity, distinct from that of viruses with the same hemagglutinin circulating in zoonotic species. Recent studies suggest that it is possible for H5N1 to acquire human type receptor specificity, but this has not occurred in nature. This review covers what is known about the molecular basis for the switch between avian and human-type receptor specificity for influenza viruses that have successfully adapted to man, the potential for H5N1 to evolve to human-type receptor specificity and its relevance to pandemic risk.


Repetitive DNA probes for the detection of Babesia equi.
This report describes DNA probes for the identification of Babesia equi. A genomic library of B. equi was constructed in pUC13. Several clones were identified that hybridized strongly to B. equi DNA. Clone pBE33 hybridized specifically to B. equi DNA and did not hybridize to horse DNA nor to DNA from Babesia caballi, Babesia bovis or Babesia bigemina. Two subclones of pBE33 (pSB20 and pEH21) containing B. equi repetitive sequences, could detect 0.49 ng and 0.97 ng B. equi DNA, respectively.


To introduce or not? Strategic analysis of hospital operations with telemedicine.
Despite its efficiency in reducing the impact of pandemics (e.g., the COVID-19), whether to introduce telemedicine as an additional way to serve chronically ill patients remains controversial for hospitals in many countries. This paper builds a stylized model to investigate a hospital's telemedicine strategy and the corresponding impacts on its operations regarding outpatient management of chronic diseases. We implement our analysis from three key concerns of the hospital in the presence of a pandemic: the differences in medical consumption and reimbursement between in-person and telemedicine modalities and the effort cost of infection reduction resulting from the pandemic. We find that in the absence of the pandemic, the hospital prefers to introduce telemedicine when the differences in medical consumption and reimbursement are both small. In the presence of the pandemic, we find that the introduction of telemedicine does not always benefit the hospital and that it is better not to introduce telemedicine in some cases since it may exacerbate the negative influence of the pandemic on the hospital's total costs. Furthermore, we surprisingly find that the hospital may set greater in-person capacity but less telemedicine capacity in response to the outbreak of the pandemic under certain conditions, which contradicts public beliefs. Finally, we show that social welfare can be improved by introducing telemedicine when the effort cost of infection reduction and the difference in reimbursement are both of moderate size. The condition under which social welfare is improved tightens with a greater difference in medical consumption.


On the importance of plasmalogen status in stimulated arachidonic acid release in the macrophage cell line RAW 264.7.
We examined the dependence of stimulated arachidonic acid release on plasmalogens using the murine, macrophage cell line 264.7 and two plasmalogen-deficient variants, RAW.12 and RAW.108. All three strains responded to unopsinized zymosan to release arachidonic acid from phospholipid stores. Arachidonic acid release appeared to be dependent on calcium-independent phospholipase A(2) activation (iPLA(2)); bromoenol lactone, a specific inhibitor of calcium-independent iPLA(2), blocked arachidonic acid release with an IC(50) of approximately 2 x 10(-7)M. Propanolol, an inhibitor of phosphatidate phosphatase, and RHC-80267, an inhibitor of diglyceride lipase, had no effect on arachidonic acid release. Arachidonic acid release in the variants displayed similar magnitude, kinetics of response and sensitivity to the inhibitors when compared to the parent strain. Arachidonic acid was released from all major phospholipid head group classes with the exception of sphingomyelin. In wild-type cells, arachidonic acid released from the ethanolamine phospholipids was primarily from the plasmalogen form. However, in the plasmalogen-deficient cells release from the diacyl species, phosphatidylethanolamine, was increased to compensate. Restoration of plasmalogens by supplementation of the growth medium with the bypass compounds sn-1-hexadecylglycerol and sn-1-alkenylglycerol had no effect on arachidonic acid release. In summary, plasmalogen status appears to have no influence on the zymosan A stimulated release of arachidonic acid from the RAW 264.7 cell line.


Rural trauma management.
Rural trauma is a major problem in the United States. Up to 70 percent of trauma fatalities occur in rural areas, even though 70 percent of the population live in urban areas. Over the past 3 decades, numerous studies have defined the concept of preventable trauma death in both rural and urban populations. With the development of a regional trauma care system in Oregon, preventable trauma mortality should decrease. An effort was made to improve the quality of trauma care in Clatsop County, Oregon, a community of 30,000 people with 2 small rural hospitals. To obtain this goal, four steps were taken: (1) physician and nurse education was improved, (2) trauma protocols promoting prompt resuscitation and stabilization of patients were established, (3) regular trauma case reviews were conducted, and (4) emergency medical technician and prehospital management were coordinated. This study reviews the trail from sporadic, uncoordinated rural trauma care to the designation process.


Cardiac hypertrophy is negatively regulated by miR-541.
Heart failure is a leading cause of death in aging population. Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading, but continuous cardiac hypertrophy is able to induce heart failure. We found that the level of miR-541 was decreased in angiotensin II (Ang-II) treated cardiomyocytes. Enforced expression of miR-541 resulted in a reduced hypertrophic phenotype upon Ang-II treatment in cellular models. In addition, we generated miR-541 transgenic mice that exhibited a reduced hypertrophic response upon Ang-II treatment. Furthermore, we found miR-541 is the target of microphthalmia-associated transcription factor (MITF) in the hypertrophic pathway and MITF can negatively regulate the expression of miR-541 at the transcriptional levels. MITF(ce/ce) mice exhibited a reduced hypertrophic phenotype upon Ang-II treatment. Knockdown of MITF also results in a reduction of hypertrophic responses after Ang-II treatment. Knockdown of miR-541 can block the antihypertrophic effect of MITF knockdown in cardiomyocytes upon Ang-II treatment. This indicates that the effect of MITF on cardiac hypertrophy relies on the regulation of miR-541. Our present study reveals a novel cardiac hypertrophy regulating pathway that was composed of miR-541 and MITF. Modulation of their levels may provide a new approach for tackling cardiac hypertrophy.


Safety and efficacy of high-rate cutoff and long detection interval ICD programming in secondary prevention patients.
Several trials demonstrated that a long detection interval and a high-rate cutoff reduced implantable cardioverter-defibrillator (ICD) therapy in primary prevention patients. However, only a few data are available for secondary prevention (SP) patients. The aim of this study was to evaluate whether these ICD programming would be effective in reducing ICD therapies in SP patients. We enrolled 65 SP patients under ICD or cardiac resynchronization therapy with the defibrillator programmed with the same setting (conventional setting). During follow-up, we changed detection rates in each zone; cycle length (CL) ≤400 to ≤370 ms for ventricular tachycardia (VT) zone, CL ≤350 to ≤320 ms for fast VT zone, CL ≤300 to ≤270 ms for ventricular fibrillation (VF) zone, and number of intervals to detect ventricular tachyarrhythmia in VF zone: 12-24. We retrospectively compared the incidences of ICD therapies, syncope, and hospitalization due to slow VT under the detection rate between both settings. Median follow-up periods were 5.0 (interquartile range 2.5-7.8) and 2.5 years (interquartile range 2.3-2.7) in conventional and strategic settings, respectively. The incidence of appropriate ATP and shock significantly decreased in strategic setting (conventional and strategic settings: 21.2 and 4.8 ATPs per year, respectively, OR 0.18, 95 % CI 0.06-0.54, p = 0.002, 26.1 and 7.8 shocks per year, respectively, OR 0.29, 95 % CI 0.09-0.88, p = 0.03). The incidence of overall inappropriate therapy significantly decreased (conventional and strategic settings: 17.6 and 2.8 therapies per year, respectively, OR 0.14, 95 % CI 0.05-0.44, p = 0.01). The incidence of syncope and slow VT was not significantly different between both settings. In conclusion, ICD programming-combined long detection interval with high-rate cutoff was effective in reducing appropriate shock and inappropriate therapy without increasing the incidence of syncope and slow VT in SP patients.


Joint effect of multiple air pollutants on daily emergency department visits in Chengdu, China.
Existing studies have typically investigated only the association between single pollutants and health outcomes. However, in the real world, people are exposed to multiple air pollutants simultaneously. The effect of air pollutants on emergency department (ED) visits has not been previously studied in the Sichuan Basin, which is one of the most polluted areas. We collected nonaccidental, respiratory and cardiovascular daily ED visits and daily concentrations of PM2.5, PMc, CO, SO2, NO2 and O3 in Chengdu, China, from 2014 to 2016. A weighted variable for the combination of multiple air pollutants was constructed to assess the joint adverse health effects. Each air pollutant was assigned a health-related weight, which indicated the pollutant's relative contribution to the joint effect. The effects on specific subpopulations (males and females; 15-65 years old and >65 years old) were also examined. With an increase of 10 μg/m3 of the combined multiple air pollutants, the daily ED visits for nonaccidental, respiratory and cardiovascular causes increased by 0.96% (95% CI: 0.51%-1.39%), 1.19% (95% CI: 0.53%, 1.85%) and 4.36% (95% CI: 1.06%, 7.76%) at lag 1, respectively. Males presented more pronounced effects, except for cardiovascular disease, than females. Elderly individuals were found to be more sensitive than young individuals. For nonaccidental and respiratory diseases, the contributions of particulate matter (PM) were dominant among the air pollutants, whereas cardiovascular disease was mainly affected by gaseous air pollutants. The combination of multiple air pollutants was significantly associated with ED visits in the Sichuan Basin, China. The joint effect of the combination of multiple air pollutants was highest for cardiovascular disease at lag 1. The relative contributions of individual pollutants varied by disease and subpopulation. These findings suggest that under different pollution scenarios, preventive strategies should target those with different diseases and different subpopulations.


Elevated maternal midtrimester serum free beta-human chorionic gonadotropin levels in vegetarian pregnancies that cause increased false-positive Down syndrome screening results.
The aim of this study was to examine whether midtrimester maternal serum free beta-human chorionic gonadotropin and alpha-fetoprotein levels for Down syndrome screening differed in vegetarian pregnancies and omnivore pregnancies and to evaluate whether maternal serum vitamin B(12) concentration affected these maker levels. Ninety-eight vegetarian and 122 omnivore singleton pregnancies were studied. Reference levels of free beta-human chorionic gonadotropin and alpha-fetoprotein were based on a population of 6312 singleton euploid pregnancies that had been surveyed previously. Serum free beta-human chorionic gonadotropin and alpha-fetoprotein levels were measured by enzyme immunoassay or radioimmunoassay. Multiples of the median values were calculated to determine whether different diet habits affected serum biomarker levels. Maternal serum vitamin B(12) levels were determined with radioimmunoassay. The free beta-human chorionic gonadotropin multiples of the median values were elevated significantly in the vegetarian pregnancies group (1.28 multiples of the median) compared with that of the reference population (1.00 multiples of the median) (P<.001). A negative association between the serum free beta-human chorionic gonadotropin multiples of the median values and the concentration of maternal serum vitamin B(12) was observed in the vegetarian pregnancies. No correlation was found between the alpha-fetoprotein multiples of the median values and the maternal serum vitamin B(12) concentration. The current data showed that the midtrimester maternal serum free beta-human chorionic gonadotropin levels increased in vegetarian pregnancies and led to an elevated false-positive rate in screening for Down syndrome compared with pregnant women with regular diet and resulted in unnecessary invasive procedures. It is necessary to establish vegetarian pregnancy alpha-fetoprotein and beta-human chorionic gonadotropin reference levels to correct increased false-positive screening results.


Migraine and obesity, is there a link?
Obesity and migraine are two frequent conditions found in the general population. In the past years, large-scale studies have established epidemiological links between the two conditions. Migraine prevalence appears to be increased in the obese population, and some characteristics of migraine are affected in the overweight population. More recent but limited data point out an improvement of migraine in the obese population after weight loss. Obesity may facilitate migraine progression to chronic daily headache or chronic migraine. Common physiological mechanisms that would be responsible for both conditions are not fully established. Several hypotheses suggest a common etiological factor for obesity and migraine. This work proposes to review the epidemiological data and to highlight the main hypotheses currently discussed.


Spatial navigation on the radial maze with trial-unique intramaze cues and restricted extramaze cues.
We investigated the use of extramaze and intramaze cues on the eight-arm radial maze. The rats received daily training consisting of forced-choice visits to four baited arms, a retention interval, and the availability of all eight arms with baits available at arms that did not appear in the forced-choice phase. The radial maze was placed in a featureless octagonal enclosure to minimize the availability of extramaze cues. Intramaze cues were provided at the distal end of each arm by placing a small object in front of the food trough; unique objects were randomly sampled from a large pool of objects. The use of extramaze and intramaze cues was assessed by rotating the objects, after the retention interval, on occasional non-rewarded probes, thereby dissociating the location of extramaze and intramaze cues. The rats used extramaze rather than intramaze cues. Implications for spatial representations are discussed.


Why is the mediterranean more readily colonized than the Red Sea, by organisms using the Suez Canal as a passageway?
Since the opening of the Suez Canal, more than 120 Red Sea species colonized the eastern Mediterranean, whereas less than 10 Mediterranean species colonized the Red Sea. For most of the species involved in this colonization, the mode of dispersal from the source to the colonized area is through free-drifting propagules. In order to examine whether the current regime of the Suez Canal may be involved in this assymetry in colonization, a mathematical hydraulic model that forecasts the direction and velocity of water currents through the year, along the length of the Canal, was utilized. The movements of free-floating propagules that occur at either entrance of the Canal, was simulated on a computer, and it was found that the completion of a Mediterranean-bound passage of Red Sea propagules is far faster and much more likely than a completion of a Red Sea-bound passage of Mediterranean propagules.


Impact of Right Ventricular Dysfunction on Short-term and Long-term Mortality in Sepsis: A Meta-analysis of 1,373 Patients.
Right ventricular (RV) dysfunction in sepsis and septic shock has been infrequently studied and has uncertain prognostic significance. Does RV function impact mortality in sepsis and septic shock? We reviewed the published literature from January 1999 to April 2020 for studies evaluating adult patients with sepsis and septic shock. Study definition of RV dysfunction was used to classify patients. The primary outcome was all-cause mortality divided into short-term mortality (ICU stay, hospital stay, or mortality ≤30 days) and long-term mortality (>30 days). Effect estimates from the individual studies were extracted and combined, using the random-effects, generic inverse variance method of DerSimonian and Laird. Ten studies, 1,373 patients, were included; RV dysfunction was noted in 477 (34.7%). RV dysfunction was variably classified as decreased RV systolic motion, high RV/left ventricular ratio and decreased RV ejection fraction. Septic shock, ARDS, and mechanical ventilation were noted in 82.0%, 27.5%, and 78.4% of the population, respectively. Patients with RV dysfunction had lower rates of mechanical ventilation (71.9% vs 81.9%; P < .001), higher rates of acute hemodialysis (38.1% vs 22.4%; P = .04), but comparable rates of septic shock and ARDS. Studies showed moderate (I2 = 58%) and low (I2 = 49%) heterogeneity for short-term and long-term mortality, respectively. RV dysfunction was associated with higher short-term (pooled OR, 2.42; 95%CI, 1.52-3.85; P = .0002) (10 studies) and long-term (pooled OR, 2.26; 95%CI, 1.29-3.95; P = .004) (4 studies) mortality. In this meta-analysis of observational studies, RV dysfunction was associated with higher short-term and long-term mortality in sepsis and septic shock.


Somatostatin Receptor 4 Agonism Normalizes Stress-Related Excessive Amygdala Glutamate Release and Pavlovian Aversion Learning and Memory in Rodents.
Excessive processing of aversive life events is a major pathology in stress-related anxiety and depressive disorders. Current pharmacological treatments have rather nonspecific mechanisms of action. Somatostatin is synthesized and released as an inhibitory co-neurotransmitter by specific GABA (gamma-aminobutyric acid) interneurons, and one of its receptors, SSTR4 (somatostatin receptor 4), is localized in brain regions involved in adaptive aversion processing and implicated in negative valence neuropathology, including the amygdala. Rat and mouse experiments were conducted to investigate effects of specific SSTR4 agonism on neurobehavioral aversion processing, including any normalization of stress-related hyperresponsiveness. A mouse experiment to investigate stress and SSTR4 agonism effects on reward processing was also conducted. In male rats (n = 5-10/group) fitted with glutamate biosensors in basolateral amygdala, SSTR4 agonism attenuated glutamate release to restraint stress in control rats and particularly in rats previously exposed to chronic corticosterone. In male mice (n = 10-18/group), SSTR4 agonism dose-dependently attenuated Pavlovian tone/footshock learning and memory measured as freezing behavior, in both control mice and mice exposed to chronic social stress, which induces excessive Pavlovian aversion learning and memory. Specificity of SSTR4 agonism effects to aversion learning/memory was demonstrated by absence of effects on discriminative reward (sucrose) learning/memory in both control mice and mice exposed to chronic social stress; SSTR4 agonism did increase reward-to-effort valuation in a dose-dependent manner and in both control mice and mice exposed to chronic social stress, which attenuates reward motivation. These neuropsychopharmacological findings add substantially to the preclinical proof-of-concept evidence for SSTR4 agonism as a treatment in anxiety and depressive disorders.


Epidermal-dermal interactions regulate gelatinase activity in Apligraf, a tissue-engineered human skin equivalent.
Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have important functions during skin development, repair and maintenance. MMP-2 and MMP-9 (gelatinase A and gelatinase B) are involved in regulating keratinocyte migration. To analyse whether Apligraf, a bilayered tissue-engineered human skin equivalent (HSE), produces gelatinases and TIMPs and whether or not epidermal-dermal interactions regulate MMP activity. The tissue distribution of MMP-2, MMP-9, TIMP-1, TIMP-2 and fibronectin was analysed by immunohistochemistry. Secreted MMP activity was quantified by a fluorimetric assay and gelatin zymography was used to monitor gelatinases in tissue culture supernatants. Apligraf expressed MMP-2 and MMP-9 and contained immunohistochemically detectable amounts of TIMP-1 and TIMP-2. The gelatinases were predominantly produced in the epidermis, whereas immunostaining of TIMP-1 and TIMP-2 was largely confined to the dermal component of the HSE. Fibronectin was expressed only in the dermis. Gelatin zymography demonstrated that intact Apligraf produced both MMP-2 and MMP-9, the latter predominantly in its latent form. Separation of the dermis from the epidermis resulted in an enhanced production and activation of MMP-9 by the epidermal layer, and secretion of latent and active MMP-2 by the dermal layer. Moreover, the incubation media of the separated epidermis demonstrated significantly stronger MMP activity than did intact Apligraf or its dermal component. These observations provide evidence that epidermal-dermal interactions suppress epidermal gelatinase activity. In addition, coexpression of TIMPs and fibronectin in the Apligraf dermis suggests that the product has the potential to counteract the imbalance between matrix production and degradation in chronic wounds and thus may support wound re-epithelialization.


Changes in leukocytes and CRP in different stages of major depression.
We recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD). We assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD: n = 82) or recurrent (RMD: n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6). Considering smoking, BMI and gender as covariates, neutrophils (FEMD: p = 0.034, RMD: p = 0.034) and CRP (FEMD: p < 0.001, RMD: p = 0.021) were higher, and eosinophils (FEMD: p = 0.005, RMD: p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0-T6 changes of neutrophil counts in FEMD (r = 0.364, p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients. These findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.


Liquid-phase oxidation of alkylaromatics by a H-atom transfer mechanism with a new heterogeneous CoSBA-15 catalyst.
A new pseudo-tetrahedral Co(II) complex has been grafted onto the surface of SBA-15 and successfully utilized for the catalytic oxidization of alkylaromatic substrates with tert-butyl hydroperoxide (TBHP)via an H-atom transfer mechanism.


Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs.
Although recombinant tissue plasminogen activator (r-tPA) is currently the most effective treatment for brain ischemic stroke, the 3-h narrow therapeutic windows severely limits its clinical efficacy. We aim to investigate the effect of resveratrol on improving treatment outcomes of delayed r-tPA administration. Patients were randomly divided according to their onset-to-treatment time (OTT), as early OTT or delayed OTT. Then, they were either treated with r-tPA + placebo or with r-tPA + resveratrol. Twenty-four hours after the treatment, outcomes were assessed with NIH stroke scale (NIHSS), and plasma levels of MMP-2 and MMP-9 were also examined with ELISA. In patients receiving delayed r-tPA treatment, co-administration of resveratrol significantly improves their treatment outcomes compared with those receiving placebo, as indicated by improved NIHSS scores. This improved outcome was be caused by resveratrol-induced reduction in plasma levels of both matrix metalloproteinase (MMP)-2 and MMP-9, as a positive correlation was observed between reductions in both MMPs and patient NIHSS scores. Resveratrol could be potentially administered as an adjuvant with r-tPA treatment, which extends the clinical therapeutic window of r-tPA, therefore improving the outcome of patients receiving late stroke treatment.


Anion inhibition studies of the dandruff-producing fungus Malassezia globosa β-carbonic anhydrase MgCA.
The genome of the fungal parasite Malassezia globosa, the causative agent of dandruff, contains a single gene annotated as encoding a carbonic anhydrase (CAs, EC 18.104.22.168) belonging to the β-class (MgCA). In an earlier work (J. Med. Chem. 2012, 55, 3513) we have validated this enzyme as an anti-dandruff drug target, reporting that sulfonamide inhibitors show in vitro and in vivo effects, in an animal model of Malassezia infection. However, few classes of compounds apart the sulfonamides, were investigated for their activity against MgCA. Here we present an anion inhibition study of this enzyme, reporting that metal complexing anions such as cyanate, thiocyanate, cyanide, azide are weak MgCA inhibitors (KIs ranging between 6.81 and 45.2 mM) whereas bicarbonate (KI of 0.59 mM) and diethyldithiocarbamate (KI of 0.30 mM) together with sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid were the most effective inhibitors detected so far, with KIs ranging between 83 and 94 μM. This study may help a better understanding of the inhibition profile of this enzyme and may offer the possibility to design new such modulators of activity belonging to different chemical classes.


[Obstetric analgesia and anesthesia in Switzerland in 1999].
This survey investigated the common practice of obstetric analgesia and anaesthesia in Swiss hospitals and evaluated the influence of the Swiss interest group for obstetric anaesthesia. In March 1999 we submitted 145 questionnaires to all Swiss hospitals providing an obstetric service. The rate of epidural analgesia (EA) was higher in large hospitals (> 1,000 births/year) than in small services. EA was maintained by continuous infusion techniques in 53% of the responding hospitals. For elective caesarean section, spinal anaesthesia (SA) and EA were performed in 77% and 16% of the patients, respectively. General anaesthesia (5%) was only used in small hospitals (< 500 births/year). Emergency caesarean section was performed under SA in 75% of all hospitals and only in 25% was a general anaesthesia used. An already existing EA for labour analgesia was continued for anaesthesia for caesarean section in 63% of Swiss hospitals. Regional anaesthesia was most commonly used for obstetric anaesthesia in Swiss hospitals. Epidemiological studies, recommendations of the Swiss interest group for obstetric anaesthesia, as well as the expectations of pregnant women, increased the numbers of regional anaesthesia compared with the first survey in 1992.


Incidence of asymptomatic meatal stenosis in children following neonatal circumcision.
To determine the incidence of meatal stenosis after neonatal circumcision. Male children (5-10 years old) who had been circumcised during the neonatal period and presented at our pediatric clinic for reasons other than urinary complaints were examined and interviewed regarding urination problems. Of the 132 cases, 27 (20.4%) had severe meatal stenosis (diameter < 5 F). Thickening of the bladder and bilateral hydronephrosis (pyelocaliceal) were found in three cases (11.1%), and a voiding cystourethrogram was performed to reveal vesicoureteral reflux (VUR). One patient had grade II VUR in his right kidney and grade III in his left kidney; another had grade II VUR in both his kidneys. These results highlight the importance of follow-up genital examination for all male children who have been circumcised during the neonatal period, to detect possible meatal stenosis.


Polyelectrolyte behaviour in mucus glycoproteins.
Mucus glycoproteins isolated from a human ovarian cyst and the sputum of a cystic fibrotic exhibit a significant decrease in reduced viscosity with increase in ionic strength, I. The molecular weights of the glycoproteins showed little variation with I, implying that the change is conformational rather than a dissociation. This change is ascribed to a polyelectrolyte-type contraction rather than to a reduction in particle asymmetry. Guanidine hydrochloride acts as a classical electrolyte in the reversible suppression of charge effects, and not as a denaturing or dissociation agent. These observations help to resolve some discrepancies in earlier studies. The occurrence of polyelectrolyte effects in these glycoproteins is ascribed to flexibility of structure and to their content of N-acetylneuraminic acid. The ionic strength values necessary for different types of physical measurement are discussed.


Mammary development in mice: effects of hemihysterectomy in pregnancy and of litter size post partum.
1. Mice were hemihysterectomized on day 8 of pregnancy to reduce the number of feto-placental units.2. Fetal mortality was not affected by hemihysterectomy; mean single-pup weight at birth was increased when compared with sham-operated controls.3. Pregnant sham-operated and hemihysterectomized animals were killed on days 13 and 18 of gestation, and their mammary glands were analysed for total DNA (DNA(t)) and RNA (RNA(t)). Both were significantly lower in the hemihysterectomized group on day 18, but not on day 13.4 Milk yield was assessed, by daily weighing of the litter, in groups of sham-operated and hemihysterectomized lactating animals suckling nine pups each. There was no difference in yield between the two groups.5. One group of sham-operated mice suckling nine pups, one of hemihysterectomized mice suckling nine pups and one of hemihysterectomized mice suckling four pups were killed on day 5 of lactation for mammary gland analysis. There was no significant difference in mammary weight or DNA(t) between the sham-operated and hemihysterectomized animals suckling nine pups, although RNA(t) was still reduced in the latter. Mammary weight, DNA(t) and RNA(t) were all significantly lower in the hemihysterectomized group suckling four pups than in either of the other two groups.6. It is concluded that the less well developed mammary glands of mice which give birth to small litters are capable of compensatory growth during the first few days of lactation if a sufficiently strong suckling stimulus is given.7. It is suggested that control of mammary development by the fetus during gestation and by the suckling young during early lactation are both mechanisms designed to ensure that milk yield is appropriate to the needs of the young.


An LC-MS-MS method for the determination of cyclizine in human serum.
Cyclizine is a piperazine derivative with anti-emetic activity that is useful in the prevention and treatment of nausea and vomiting associated with motion sickness. A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method is presented for the quantitation of cyclizine in serum. Sample pretreatment involved liquid-liquid extraction of 200 microl of serum with dichloromethane after the addition of 100 microl each of ammonium hydroxide and internal standard solutions. The extracts were analyzed by HPLC on a Luna C18 reversed-phase column and an ion-trap mass spectrometer with an electrospray interface. A limit of detection of 1 ng/ml was determined which allowed for the reliable measurement of cyclizine in the serum of human subjects. The method was found to be linear over the calibration range of 2.5-100 ng/ml. The applicability of this method was demonstrated by the analysis of serum obtained from a human volunteer following administration of a single 50 mg cyclizine hydrochloride tablet. The reported method was observed to have the necessary sensitivity, selectivity, precision and accuracy for monitoring cyclizine concentrations in human subjects following oral administration.


Leptomeningeal metastases from recurrent squamous cell cancer of the skin.
We report two patients with leptomeningeal metastases from squamous cell cancer of the skin. In one patient cauda equina metastases appeared 6 years after initial presentation; the tumor from radical neck dissection demonstrated perineural invasion suggesting a possible route for subarachnoid dissemination. The other patient presented 2 years after initial diagnosis with confusion and cranial nerve seven and twelve palsies. Both patients died from complications of leptomeningeal metastases.


High-Resolution Ion Microscope Imaging over Wide Mass Ranges Using Electrodynamic Postextraction Differential Acceleration.
A time-dependent postextraction differential acceleration (PEDA) potential was used to temporally focus increasingly heavy ions in a stigmatic imaging mass spectrometer, allowing them to be imaged with high mass and spatial resolutions over a broad mass-to-charge (m/z) range. By applying a linearly rising potential to the ion extraction electrode, sequential m/z ratios were subjected to a changing electric field, allowing their foci to coincide at the detector. Using this approach, at least 75% of the maximum mass resolution was obtained over a 300-600 Da range when the ion microscope was focused around 450 Da, representing more than a 10-fold increase over the conventional single-field PEDA method.


Evaluation of multiple muscle loads through multi-objective optimization with prediction of subjective satisfaction level: illustration by an application to handrail position for standing.
Proposed here is an evaluation of multiple muscle loads and a procedure for determining optimum solutions to ergonomic design problems. The simultaneous muscle load evaluation is formulated as a multi-objective optimization problem, and optimum solutions are obtained for each participant. In addition, one optimum solution for all participants, which is defined as the compromise solution, is also obtained. Moreover, the proposed method provides both objective and subjective information to support the decision making of designers. The proposed method was applied to the problem of designing the handrail position for the sit-to-stand movement. The height and distance of the handrails were the design variables, and surface electromyograms of four muscles were measured. The optimization results suggest that the proposed evaluation represents the impressions of participants more completely than an independent use of muscle loads. In addition, the compromise solution is determined, and the benefits of the proposed method are examined.


Direct gas chromatographic analysis of cyclic N-nitrosamines.
A rapid gas chromatographic technique has been developed for quantitative estimation of cyclic N-nitrosamines. Cumbersome clean-up procedures are unnecessary and quantitative estimation can be done by injecting hexane extract without further pretreatment. The detection limit for the procedures is ca. 0.5 ng.


Purinergic receptor distribution in endothelial cells in blood vessels: a basis for selection of coronary artery grafts.
Expression levels of the purinergic P2X receptor subunits (P2X(1) to P2X(7)) and P2Y(2) were examined in the endothelial cell layer of internal mammary artery (Ann. Thorac. Surg. 54 (1992) 652), radial artery (Ann. Thorac. Surg. 16 (1973) 111) and saphenous vein (Ann. Thorac. Surg. 20 (1975) 628) samples obtained at surgery for coronary artery bypass grafts using immunohistochemistry and confocal microscopy. Similar levels of P2X(1), P2X(2), P2X(3), P2X(7) and P2Y(2) were found in the endothelial cells in all vessels examined while the levels of P2X(5) and P2X(6) were uniformly lower. A clear difference was measured in P2X(4) expression between arteries and veins. Both radial and internal mammary arteries exhibited very low levels of P2X(4) whereas the level in the saphenous vein was 14.6 fold higher (P<0.0001), approaching that of the major receptor subtypes. These data showing strong expression of P2X(4) in veins have implications for the choice of vessels used in coronary artery bypass grafts given that P2X(4) is involved in calcium influx into endothelial cells, modulates blood vessel contractility and is up-regulated in situations involving intima proliferation suggesting vein grafts are more susceptible to developing atherosclerosis.


Development and evaluation of new zwitterionic hydrophilic interaction liquid chromatography stationary phases based on 3-P,P-diphenylphosphonium-propylsulfonate.
New zwitterionic stationary phases were synthesized by covalently bonding 3-P,P-diphenylphosphonium-propylsulfonate to silica gel. The resulting materials possess both a negatively charged sulfonate group and a positively charged quaternary phosphonium group, which means that there is no net charge over a wide pH range. The retention mechanism and chromatographic behavior of polar solutes under HILIC conditions were studied on these zwitterionic phases. Compared to the commercial ZIC-HILIC column and a bare silica gel stationary phase, the newly synthesized zwitterionic stationary phases provided greater retention, higher peak efficiency and better peak symmetry in the HILIC mode. The analytes examined included: β-blockers, nucleic acid bases and nucleosides, salicylic acid and its analogues, and water soluble vitamins. Factors, such as the type of organic modifiers, solvent composition, pH and the buffer concentration of the mobile phase, have been considered as potential variables for controlling the chromatographic retention of polar analytes.


LH (as HCG) and FSH surges for final oocyte maturation: sometimes it takes two to tango?
Until now, clinicians have been relying solely on LH activity-dependent triggering of final oocyte maturation and thus taken it for granted that the natural midcycle FSH surge is biologically redundant. However, it is time to question this paradigm. Evidence from clinical studies hint that in a yet-to-be-defined subset of patients, dual LH and FSH surge is advantageous compared with LH-only surge in the form of human chorionic gonadotrophin (HCG) trigger. Dual surge can be triggered by a bolus of gonadotrophin-releasing hormone agonist causing a flare-up of both endogenous LH and FSH, resembling the natural midcycle surge of gonadotrophins. HCG given in parallel secures adequate exposure to LH activity. Further research is needed to characterize the patients in whom FSH surge is needed for proper resumption of the oocyte meiotic process.


Superficial bladder cancer treated with intravesical bacillus Calmette-Guérin or adriamycin: follow-up report.
We evaluated 139 patients with superficial bladder cancer (Stages Ta, Tl, and TIS) and treated them with either intravesical bacillus Calmette-Guérin, Tice strain (BCG), or doxorubicin hydrochloride (Adriamycin [ADR]) in a nonrandomized, multicenter study. Our follow-up study comprises 135 of these patients. Of these patients, 78 tumors were completely resected, and 61 were incompletely resected. When a proportional-hazards model (Cox) was applied, there was a statistically significant difference between the recurrence rates for the two drugs. On the basis of recurrence rates per 100 patient-months, both BCG (1.2) and ADR (0.9) worked well with completely resected tumors. However, for incomplete resections, the recurrence rate for BCG (0.9) was less than half that for ADR (1.9). The overall recurrence rates were 1.1 and 1.3 for BCG and ADR, respectively. There have been 42 failures of treatment with either BCG or ADR. We defined failure as any recurrence of tumor; progression of the cancer in stage, grade, tumor number or size; or any residual tumor after 18 treatments (14 months of therapy). As to the failures in patients whom we followed up, and whose treatment was either switched from ADR to BCG or continued on further BCG treatment, 53 per cent have achieved complete remission. Complete remission for BCG and ADR were 76 per cent and 52 per cent, respectively. Of the various factors considered in the study, only tumor grade and treatment drug were statistically significant. The cystectomy rate was 1 per cent for BCG-treated patients and 0 for ADR-treated patients.


Relation of BAALC and ERG Gene Expression with Overall Survival in Acute Myeloid Leukemia Cases.
The objectives of this study were to evaluate the expression of brain and acute leukemia, cytoplasmic (BAALC) gene and erythroblast transformation-specific related gene (ERG) in de novo cases of acute myeloid leukemia (AML) and identify roles in disease progression and outcome. This study included 50 newly diagnosed AML patients, along with 10 apparently healthy normal controls. BAALC and ERG expression was detected in the bone marrow of both patients and controls using real-time RT-PCR. BAALC and ERG expression was detected in 52% of cases but not in any controls. There was a statistically significant correlation between BAALC and ERG gene expression and age (p- value=0.004 and 0.019, respectively). No statistical significance was noted for sex, lymphadenopathy, hepatomegaly, splenomegaly, other hematological findings, immunophenotyping and FAB sub-classification except for ERG gene and FAB (p-value=0.058). A statistical significant correlation was found between response to treatment with ERG expression (p-value=0.028) and age (p-value=0.014). A statistically significant variation in overall survival was evident with patient age, BM blast cells, FAB subgroups, BAALC and ERG expression (p-value= <0.001, 0.045, 0.041, <0.008 and 0.025 respectively). Our results suggest that BAALC and ERG genes are specific significant molecular markers in AML disease progression, response to treatment and survival.


On Aethina Erichson of Northeast India (Coleoptera: Nitidulidae: Nitidulinae).
Four species of Aethina [Aethina (Aethina) vicina Grouvelle, 1894, Aethina (Idaethina) orientalis (Nietner, 1856), Aethina (Idaethina) subrugosa (Grouvelle, 1894b) and Aethina (Circopes) subquadrata (Motschulsky, 1858)] have been newly recorded from northeast Indian states. Hitherto, three species, viz., Aethina (Aethina) argus Grouvelle, 1890, Aethina (Aethina) cyaneipennis Grouvelle, 1903 and Aethina (Aethina) inconspicua Nakane, 1967 were known from Northeast India. The specific status of Aethina (Aethina) nigrocastanea Grouvelle, 1903 has been reestablished. Altogether eight species of Aethina are treated in this paper. The paper incorporates redescriptions of the genus, and species of Aethina from Northeast India with a key to these species.


Reconstructive utility of the bilobed flap: lessons from flap successes and failures.
Although the bilobed transposition flap's utility in the reconstruction of difficult facial surgical wounds is often praised, the complicated design of the flap can produce unacceptable esthetic results if the nuances of flap design and execution are not properly understood. To review the historical development of the bilobed flap and to offer contemporary suggestions on how to manipulate the flap's design to improve the flap's performance. Illustrative case examples of bilobed flap successes and failures are appropriately and thoroughly examined. The proper use of the bilobed flap completely depends on understanding the design modifications of the flap that can impact the flap's final appearance. The bilobed flap, with its complicated design and requirement of meticulous operative technique, introduces tremendous opportunities for esthetic misadventure. Nonetheless, the flap, when properly constructed, deserves its reputation as the reconstructive flap of choice for many difficult wounds, particularly those wounds located on the distal nose.


Umeclidinium in patients with COPD: a randomised, placebo-controlled study.
Efficacy and safety of umeclidinium administered in a dry power inhaler were evaluated in moderate-to-very-severe chronic obstructive pulmonary disease patients. This was a randomised, placebo-controlled study assessing once-daily umeclidinium 62.5 and 125 μg over 12 weeks. The primary end-point was change from baseline in trough forced expiratory volume in 1 s (FEV1) on day 85. Secondary end-points were 0-6-h weighted mean and serial forced expiratory volume in 1 s. Other end-points were transitional dyspnoea index, health outcomes (St George's Respiratory Questionnaire), pharmacokinetics and safety. 246 patients were enrolled; 168 completed the study. On day 85, umeclidinium 62.5 and 125 μg significantly improved least squares mean change from baseline in trough FEV1 (127 and 152 mL, respectively; p<0.001) compared with placebo. On day 84, umeclidinium 62.5 and 125 μg significantly improved least squares mean change from baseline in 0-6-h weighted mean (166 and 191 mL, respectively; p<0.001) and serial FEV1 at each time point (p≤0.003). Significant improvements in least squares mean transitional dyspnoea index focal score for UMEC 125 mg(1.3 units; p,0.05) and change from baseline St George's Respiratory Questionnaire total score for both UMEC doses (-7.9 and -10.87 units, for UMEC 62.5 mg and 125 mg, respectively; both p,0.001) were noted compared with placebo at week 12 [DOSAGE ERROR CORRECTED].The incidence of adverse events was low and similar across treatments. Umeclidinium 62.5 and 125 μg significantly improved lung function, dyspnoea and health status compared with placebo, and were well tolerated in chronic obstructive pulmonary disease patients over 12 weeks.


Assessment of lung doses in patients undergoing total body irradiation for haematological malignancies with and without lung shielding.
Total body irradiation (TBI) practices vary considerably amongst centres, and the risk of treatment related toxicities remains unclear. We report lung doses for 142 TBI patients who underwent either standing TBI with lung shield blocks or lying TBI without blocks. Lung doses were calculated for 142 TBI patients treated between June 2016 and June 2021. Patients were planned using Eclipse (Varian Medical Systems) using AAA_15.6.06 for photon dose calculations and EMC_15.6.06 for electron chest wall boost fields. Mean and maximum lung doses were calculated. Thirty-seven patients (26.2%) were treated standing using lung shielding blocks with 104 (73.8%) treated lying down. Lowest relative mean lung doses were achieved using lung shielding blocks in standing TBI, reducing the mean lung doses to 75.2% of prescription (9.9 Gy), ±4.1% (range 68.6-84.1%) for a prescribed dose of 13.2 Gy in 11 fractions, including contributions from electron chest wall boost fields, compared to 12 Gy in 6 fraction lying TBI receiving 101.6% mean lung dose (12.2 Gy) ±2.4% (range 95.2-109.5%) (P ≪ 0.05). Patients treated lying down with 2 Gy single fraction received the highest relative mean lung dose on average, with 108.4% (2.2 Gy) ±2.6% of prescription (range 103.2-114.4%). Lung doses have been reported for 142 TBI patients using the lying and standing techniques described herein. Lung shielding blocks significantly reduced mean lung doses despite the addition of electron boost fields to the chest wall.


Beyond empathy decline: Do the barriers to compassion change across medical training?
Despite being a mandated, foundational value in healthcare, research on compassion remains limited. Studying the individual, patient, clinical, and contextual factors that interfere with compassion-the "barriers"-may clarify our understanding of the origins of compassion and identify potential targets for improving patient-centred care. Studies of the related construct of empathy have suggested that medical students report declines with increasing clinical experience. In contrast, when comparing physicians with medical students, increased clinical experience predicts lower barriers to compassion. Whether-and how-a similar experience-related decline in the factors that interfere with compassion occurs across medical training remains unknown. To describe how the barriers to compassion vary across clinical training in medical students. New Zealand medical students (N = 351) in their clinical years (Years 4-6) completed measures of the Barriers to Physician Compassion (BPCQ) and potential covariates such as demographics, work burden factors, and dispositional factors. The BPCQ indexes the extent to which barriers in four domains (individual, patient, clinical, and contextual) interfere with a physician/student's compassion towards patients. Analyses of variance and regression analyses were used to explore the effect of year level on the four types of barriers. Year 4 students reported slightly lower student-related, environmental and patient/family-related (but not clinical) barriers than Year 6 students (effect size: ɷ2 < 0.05); all barriers increased comparably across training. Controlling for relevant confounds, regression analyses confirmed that lower year level predicted lower barriers to compassion. Higher self-compassion, but not gender, predicted lower barriers. In extending studies of empathy decline, this report suggests that students experience higher barriers to compassion as clinical training progresses. This is in contrast to existing studies contrasting physicians with medical students, where greater experience was associated with lower perceived barriers to compassion. Self-compassion may offset increases in barriers to care.


The effect of body mass index on surgical outcomes and survival following pelvic exenteration.
We sought to evaluate whether preoperative body mass index (BMI) impacts surgical outcomes, complication rates, and/or recurrence rates in women undergoing pelvic exenteration. All women who underwent pelvic exenteration for gynecologic indications at our institution from 1993 through 2010 were included. Women were stratified into 3 groups based on BMI. Baseline characteristics, surgical outcomes, early (<60 days) and late (≥ 60 days) postoperative complications, and recurrence/survival outcomes were collected. Multivariate logistic regression analyses were performed. Kaplan-Meier survival curves were compared using log-rank test. 161 patients were included (59 normal weight, 44 overweight, 58 obese). Median follow-up times were 22, 29, and 25 months. Most patients underwent total pelvic exenteration (68%); 64.6% had a vaginal reconstruction. On multivariate analysis, both overweight and obese patients had a higher risk of early superficial wound separation compared to normal weight patients - OR 10.74 (3.33-34.62, p<0.001) and OR 4.35 (1.40-13.52, p=0.011), respectively. Length of surgery was significantly longer for overweight (9.6h, OR 1.26, 1.02-1.55, p=0.032) and obese (10.1h, OR 1.24, 1.04-1.47, p=0.014) patients than for normal weight patients (8.7h). Late postoperative complications for patients in the normal weight, overweight, and obese groups were 47.5%, 45.5%, and 43.1% (p=0.144). There were no differences in time to recurrence (p=0.752) or overall survival (p=0.103) between groups. Although operative times were longer and risk for superficial wound separation was significantly higher, pelvic exenteration appears to be feasible and safe in overweight and obese women with overall complication rates and survival outcomes comparable to normal weight women.