Acute and long-term effects of ACE inhibition on renal haemodynamics in glomerular and interstitial nephropathies.
Angiotensin-converting enzyme (ACE) inhibitors are the drugs of choice for the treatment of hypertension in patients with non-diabetic nephropathies. However, not every trial has reported better results with ACE inhibitors (ACE-I) than with other drugs. This study investigates whether the acute and chronic effects of ACE inhibition on renal and glomerular haemodynamics are similar in glomerular and interstitial nephropathies. We studied 20 hypertensive patients, on their usual diet, with mild-to-moderate chronic renal failure secondary to non-diabetic nephropathy. After a three-week wash out period, we determined plasma clearances of para-amino-hippurate and inulin before, and after acute oral administration of either enalapril or ramipril. This same test was carried out after one and two years of treatment with the same drug. Acute ACE inhibition causes a decrease of renal perfusion, glomerular filtration and pressure with an increase of afferent resistances. Long-term ACE inhibition is associated only with a decrease in renal perfusion, with a non-significant tendency to higher filtration fraction and lower afferent resistances. All the renal haemodynamic modifications mentioned above are present only in patients with glomerular diseases. Renal and glomerular haemodynamic responses are not similar after acute and chronic ACE inhibition. Only patients with glomerular diseases show acute or long-term responses to ACE inhibition.


Nucleosome rearrangement in human cells following short patch repair of DNA damaged by bleomycin.
We have examined the structure of newly repaired regions of chromatin in intact and permeabilized human cells following exposure to bleomycin (BLM). The average repair patch size (in permeabilized cells) was six to nine bases, following doses of 1-25 micrograms/mL BLM, and greater than 80% of the total repair synthesis was resistant to aphidicolin. In both intact and permeabilized cells, nascent repair patches were initially very sensitive to staphylococcal nuclease, analogous to repair induced by "long patch" agents, and are nearly absent from isolated nucleosome core DNA. Unlike long patch repair, however, the loss of nuclease sensitivity during subsequent chase periods was very slow in intact cells, or in permeabilized cells treated with a low dose of BLM (1 microgram/mL), and was abolished by treatment with hydroxyurea (HU) or aphidicolin (APC). The rate of repair patch ligation did not correlate with this slow rate of chromatin rearrangement since greater than 95% of the patches were ligated within 6 h after incorporation (even in the presence of HU or APC). In permeabilized cells, repair patches induced by either 5 or 25 micrograms/mL BLM, where significant levels of strand breaks occur in compact regions of chromatin, lost the enhanced nuclease sensitivity at a rate similar to that observed following long patch repair. This rapid rate of rearrangement was not affected by APC. These results indicate that short patch repair in linker regions of nucleosomes, and/or "open" regions of chromatin, involves much less nucleosome rearrangement than long patch repair or short patch repair in condensed chromatin domains.


Adjuvant chemotherapy in curatively resected rectal cancer: How valid are the data?
According to the result of the Cochrane review published in 2012, postoperative adjuvant chemotherapy (CTx) is associated with a survival benefit for rectal cancer patients operated for cure in comparison to patients who underwent only the surgical resection. To analyze the quality of the data supporting the advantage of adjuvant CTx after surgery for rectal cancer. In the times of increasing health care costs, it is imperative to offer the patient an evidence-based therapy that justifies potential side effects as well as costs. Overall survival was selected as endpoint of interest. Among the 21 included papers which analyzed this endpoint, we identified those three publications which have the highest weights to influence the final result. The validity of these papers was analyzed using the CONSORT checklist for randomized controlled trials. We performed a second meta-analysis excluding the three analyzed studies (n = 18) in order to assess their impact on the overall result of the original meta-analysis. Finally, we performed a third meta-analysis excluding all studies (n = 16) which showed a statistically improved overall survival. The detailed analysis of the three most relevant RCTs according to the items of the CONSORT checklist showed several pitfalls. In up to 47% of the items, inappropriate answers were found. Generally, a lack of information regarding the randomization procedure as well as the absence of allocation concealment, blinded set-up, of intention-to-treat analysis and omission of sample size calculation were common problems of the analyzed studies. The exclusion of these three studies from the meta-analysis did not affect the general result of the meta-analysis, still confirming a survival advantage after adjuvant chemotherapy. After exclusion of single studies with a statistically significant outcome improvement, the meta-analysis of the remaining 16 studies again shows a statistically significant result due in part to a large remaining sample size. The three most powerful publications show substantial deficits. We suggest a more critical appraisal regarding the validity of single studies because a meta-analysis cannot overcome the limitations of individual trials by pooling treatment effect estimates to generate a single best estimate.


The importance of brain temperature in patients after severe head injury: relationship to intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and outcome.
Brain temperature was continuously measured in 58 patients after severe head injury and compared to rectal temperature, intracranial pressure, cerebral blood flow, and outcome after 3 months. The temperature difference between brain and rectal temperature was also calculated. Mild hypothermia (34-36 degrees C) was also used to treat uncontrollable intracranial pressure (ICP) above 20 mm Hg when other methods failed. Brain and rectal temperature were strongly correlated (r = 0.866; p < 0.001). Four groups were identified. The mean brain temperature ranged from 36.9 +/- 0.4 degrees C in the normothermic group to 38.2 +/- 0.5 degrees C in the hyperthermic group, 35.3 +/- 0.5 degrees C in the mild therapeutic hypothermia group, and 34.3 +/- 1.5 degrees C in the hypothermia group without active cooling. The mean DeltaT(br-rect) was positive for patients with a T(br) above 36.0 degrees C (0.0 +/- 0.5 degrees C) and negative for patients during mild therapeutic hypothermia (-0.2 +/- 0.6 degrees C) and also in those with a brain temperature below 36 degrees C without active cooling (0.8 +/- -1.4 degrees C) - the spontaneous hypothermic group. The cerebral perfusion pressure (CPP) was increased significantly by active cooling compared to the normothermic and hyperthermic groups. The mean cerebral blood flow (CBF) in patients with a brain temperature between 36.0 degrees C and 37.5 degrees C was 37.8 +/- 14.0 mL/100 g/min. The lowest CBF was measured in patients with a brain temperature <36.0 degrees C and a negative brain-rectal temperature difference (17.1 +/- 14.0 mL/100 g/min). A positive trend for improved outcome was seen in patients with mild hypothermia. Simultaneous monitoring of brain and rectal temperature provides important diagnostic and prognostic information to guide the treatment of patients after severe head injury (SHI) and the wide differentials that can develop between the brain and core temperature, especially during rapid cooling, strongly supports the use of brain temperature measurement if therapeutic hypothermia is considered for head injury care.


Comparison of the Immunogenicity of Four Infectious Bursal Disease Intermediate Vaccines in Commercial Broiler Flocks in Iran: A Field Trial Study.
Infectious bursal disease (IBD) is a highly contagious disease in young chickens worldwide. The major strategy for the prevention and control of IBD virus (IBDV) is vaccination. Therefore, the present study aimed to compare the immunogenicity of four commercially available IBD vaccines on broilers (Ross 308) that were raised in areas with very virulent IBDV infection history. Two commercial broiler farms with four standard poultry houses were selected in Alborz (n=6,250 birds per house) and Khorasan Razavi (n=8,000 birds per house) provinces of Iran. In each farm, the houses were randomly assigned to one of the four IBD intermediate vaccine brands including Dn, Vc, Ch, and Razi. The birds in Alborz were vaccinated against IBDV via drinking water at 18 and 22; and 15 and 21 days of age in Alborz and Khorasan Razavi flocks, respectively. The enzyme-linked immunosorbent assay antibody titers against IBDV were measured in 20 birds per group at 1, 28, 35, and 42 days of age. In addition, production attributes including body weight, feed conversion ratio, mortality, and production index were measured during the research period. According to the findings, the IBD antibody titers were not affected by the vaccine brands at 28, 35, and 42 days of age (P>0.05). Following the second IBD vaccination, an increasing trend in IBD antibody titers was noted in the Razi vaccine as well as other brands at days 35 and 42 compared to the previously recorded titers (P<0.05). Moreover, the production attributes of the flocks receiving various IBDV vaccine brands were not different (P>0.05). Regarding the productivity indices and high immunogenicity levels, the results indicated that the potential of the IBD Razi vaccine was comparable to the other investigated brands of commercial IBD vaccines, and nominated it as an immunogenic candidate vaccine for use in commercial broilers.


Expanding therapeutic options in mantle cell lymphoma.
Mantle cell lymphoma (MCL) still carries a poor prognosis. Chemoimmunotherapy (combination with rituximab) is the routine first-line therapy, although data strongly suggest a benefit from intensification through high-dose therapy with stem cell transplantation consolidation or dose-intense chemotherapy with HyperCVAD (fractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone)/rituximab. Unfortunately, most patients still experience relapse, and a multitude of novel agents are currently being tested in this setting, including proteasome inhibitors with bortezomib (the first of its class and first Food and Drug Administration-approved drug in MCL), mammalian target of rapamycin inhibitors, Bcl-2 inhibitors, and antiangiogenesis agents, among others. Because of the relative rarity of the disease-MCL represents 6% of non-Hodgkin lymphoma-an obvious effort is needed to enroll patients on clinical trials. Not surprisingly, as in other non-Hodgkin lymphomas, MCL appears more and more as a heterogeneous disease, which might impact future clinical trial design through pharmacogenomics and hopefully help us develop smaller "molecular" relevant trials.


Properties of yeast expressed Aspergillus nidulans chitin synthase B which is essential for hyphal growth.
A complementary DNA of the Aspergillus nidulans chsB gene encoding chitin synthase, an essential gene for hyphal growth, was obtained by RT-PCR and expressed in Saccharomyces cerevisiae by using the GAL1 promoter in a multicopy plasmid. The biochemical characteristics of chitin synthase B (ChsB) expressed in S. cerevisiae were examined. The chitin synthase B produced in galactose medium showed zymogenicity due to activation by trypsin treatment and required Mg2+ ion to exert maximal activity. It was competitively inhibited by polyoxin D. The Ki value of the inhibitor was 10 microM, and the K(m) for the substrate was 1.6 mM. The activity was enhanced by the addition of N-acetylglucosamine. The optimal pH is 7.5 when Mg2+ is used. These characteristics are the same as those of other chitin synthases.


A case report: reconstruction of a damaged knee following treatment of giant cell tumor of the proximal tibia with cryosurgery and cementation.
Reconstruction of a knee damaged by cement packed to cure a giant-cell tumor is sometimes difficult. We reconstructed such a knee by removal of the cement, autologous bone transplantation and distraction osteogenesis using the Ilizarov apparatus. In this paper the results 29 months after the salvage surgery are given. We saw a 31-year-old woman's knee joint that showed osteoarthritic change after curettage, cryosurgery and cementation performed 4 years previously for a giant-cell tumor of the proximal tibia. We reconstructed the knee joint. This procedure included cement removal, alignment correction by tibial osteotomy, subchondral bone reconstruction by autologous bone transplantation, and filling the defect after removing the bone cement by elongating the diaphysis using the Ilizarov apparatus. Distraction was terminated 4 months later when 54 mm of elongation was performed. All devices were removed 12 months after the surgery. Seventeen months after the removal of the apparatus, the range of motion of the right knee was 0 degrees extension and 110 degrees flexion, and the patient was able to walk without pain. Although the treatment period is long and there may be some complications of Ilizarov lengthening and distraction osteogenesis, this procedure has numerous benefits. Bony defects can be soundly reconstructed and, at the same time, the alignment of the knee can be corrected. Also it is not necessary to reconstruct the ligaments because the insertions are intact. If osteoarthritis progresses, a surface type total knee replacement can be performed, not constrained type prosthesis, which would be used if the bony structure had not been reconstructed. This procedure may be one of the candidates for reconstructing such knee joints destroyed by bone cement.


A rare large cutaneous chondroid syringoma involving a toe: A case report.
Chondroid syringoma (CS) occurs mostly on the face and neck, and rarely occurs in the toe. Malignant CS is invasive, grows quickly, and has a high recurrence rate. The presence of a bilobed CS in 1 toe has never been reported in the literature. A 72-year-old male patient presented with a mass in a third toe of his right foot. The mass had slowly grown in 2 years. He felt mild pain and the mass occupied most of the tip of the toe. Radiographs showed a large soft-tissue mass in the third toe of his right foot without any bone destruction. Ultrasonogram showed 2 partly fused hypoechoic masses within the lesion. The mass was therefore diagnosed as a benign CS. We amputated the toe with the mass under local anesthesia. The postoperative pathohistological examinations confirmed that the lesion was a bipartite CS exhibiting active cellular proliferation. Two years after surgery, there was no tumor recurrence. CS can also present as multiple adjacent masses. Complete surgical resection and long-term follow-up are essential.


Differential impact of birth weight and early growth on neonatal mortality in puppies.
Breeding kennels face a high rate of neonatal mortality, on which the impact of nutrition remains to be determined. This study was designed to evaluate the impact of birth weight (reflecting intrauterine growth) and early growth rate (reflecting colostrum intake) on risk of neonatal mortality in puppies and to determine the critical thresholds of both parameters. Puppies from various breeds were weighed at birth ( = 514) and at 2 d of age, and the growth rate over that period (early growth rate) was calculated for all survivors ( = 477). Linear mixed models evaluated the effect of birth weight on mortality between birth and 2 d of age and the effect of both birth weight and early growth rate on mortality between 2 and 21 d of age. Birth weight was influenced by litter size ( = 0.003), with more low-birth-weight puppies (the lightest 25% within a breed size) in large litters compared with smaller litters. Mortality over the first 2 d after birth was associated with birth weight ( < 0.001), with 81.1% of dying puppies characterized by a low birth weight. Mortality between 2 and 21 d of age was not related to birth weight but was found to be associated with early growth rate ( < 0.001), with higher risk of death in puppies with growth rate at or below -4% after the first 2 d of life. This study demonstrates the differential effect of intrauterine nutrition impacting mortality during the first 2 d of life and that of colostrum intake impacting mortality until 21 d of life. Birth weight and early growth rate thresholds provided in this study allow identification of puppies at risk, whereby provision can be made for adequate nursing to increase their chances to survive.


Risk Factors, Presentation, and Outcome in Acute Stroke according to Social Position Indicators in Patients Hospitalised in a Referral Centre in Bogotá 2011-2019.
Treatment of stroke is time-dependent and it challenges patients' social and demographic context for timely consultation and effective access to reperfusion therapies. The objective of this study was to relate indicators of social position to cardiovascular risk factors, time of arrival, access to reperfusion therapy, and mortality in the setting of acute stroke. A retrospective analysis of patients with a diagnosis of ischaemic stroke in a referral hospital in Bogotá was performed. A simple random sample with a 5% margin of error and 95% confidence interval was selected. Patients were characterised according to educational level, place of origin, marital status, occupation, duration of symptoms before consultation, cardiovascular risk factors, access to reperfusion therapy, and mortality during hospitalisation. 558 patients were included with a slight predominance of women. Diagnosis of diabetes was more common in women and smoking in men (n = 68, 28.4% vs. n = 51, 15.9%; p = 0.0004). Rural origin was associated with higher prevalence of hypertension, diabetes, and dyslipidaemia (hypertension n = 45, 73.8% vs. n = 282, 57.4%; p = 0.007; diabetes n = 20, 33.3% vs. 109, 19.5%; p = 0.02; dyslipidaemia n = 19, 32.7% vs. n = 93, 18.9%; p = 0.02). Mortality was higher in rural patients (n = 8, 14.2% vs. n = 30, 6.1%; p = 0.03). Lower schooling was associated with higher frequency of hypertension and dyslipidaemia (hypertension n = 152, 76.0% vs. n = 94, 46.3%; p ≤ 0.0001; dyslipidaemia n = 56, 28% vs. n = 35, 17.0%; p = 0.009) as well as with late consultation (n = 30, 15% vs. n = 59, 28.7%; p = 0.0011) and lower probability of accessing reperfusion therapy (n = 12, 6% vs. n = 45, 22%; p ≤ 0.0001). Formal employment was associated with a visit to the emergency department in less than 3 h (n = 50, 25.2% vs. n = 58, 18%, p = 0.04 and a higher probability of accessing reperfusion therapy (n = 35, 17.6% vs. n = 33, 10.2%; p = 0.01). Finally, living in a household with a stratum higher than 3 was associated with a consultation before 3 h (n = 77, 25.5% vs. n = 39, 15.6%; p = 0.004) and a higher probability of reperfusion therapy (n = 57, 18.9% vs. n = 13, 5.2%; p ≤ 0.0001). Indicators of socio-economic status are related to mortality, consultation time, and access to reperfusion therapy. Mortality and reperfusion therapy are inequitably distributed and, therefore, more attention needs to be directed to the cause of these disparities in order to reduce the access gap in the context of acute stroke in Bogotá.


Premenstrual dysphoric disorder--review of actual findings about mental disorders related to menstrual cycle and possibilities of their therapy.
It is known that mood disorders in women explicitly relates to estrogen production. Except for these findings phenomenon as Premenstrual Syndrome and Premenstrual Dysphoric Disorder, directly connected to menstrual cycle in women, is widely discussed. Premenstrual dysphoric disorder (PMDD) is a set of subjectively unpleasant mental and somatic symptoms. It appears in luteal phase of ovarian cycle. During menstruation it remits and disappears up to one week from its termination. DSM IV classified PMDD into the category of "Other specific depressive disorders" and further revision DSM IV-TR classifies PMDD as a separate strictly defined psychiatric diagnosis. The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) does not include any specific category as PMDD or similar. The closest category F38.8 does not represent the core of the phenomenon because it relates only to general depressive symptomatology and does not give specific diagnostic criteria to menstrual cycle related mood disorders (Grady-Weliky, 2003). In the presented article, possible effectivity of PMDD treatment with the focus to antidepressants of SSRI type (Serotonin selective reuptake inhibitors) is discussed. In spite of interesting and significant findings, the treatment of PMDD and accordingly PMS is above all multidisciplinary question and it must be treated like that.


Urinary bile acid and bile alcohol excretion does not reflect the genetic polymorphism of debrisoquine hydroxylation.
Excretion of the major urinary bile alcohol 27-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24,25- pentol , and of cholic, chenodeoxycholic, deoxycholic and lithocholic acid was measured in 24 h urine collections of 10 extensive and seven poor metabolizers of debrisoquine. There was no significant difference of the excretion of these cholesterol metabolites between the two groups, indicating that cholesterol hydroxylation to bile alcohols and bile acids is probably not controlled by the same genes responsible for the 'debrisoquine-type' hydroxylation polymorphism.


Assessing the chances of success: naïve statistics versus kind experience.
Additive integration of information is ubiquitous in judgment and has been shown to be effective even when multiplicative rules of probability theory are prescribed. We explore the generality of these findings in the context of estimating probabilities of success in contests. We first define a normative model of these probabilities that takes account of relative skill levels in contests where only a limited number of entrants can win. We then report 4 experiments using a scenario about a competition. Experiments 1 and 2 both elicited judgments of probabilities, and, although participants' responses demonstrated considerable variability, their mean judgments provide a good fit to a simple linear model. Experiment 3 explored choices. Most participants entered most contests and showed little awareness of appropriate probabilities. Experiment 4 investigated effects of providing aids to calculate probabilities, specifically, access to expert advice and 2 simulation tools. With these aids, estimates were accurate and decisions varied appropriately with economic consequences. We discuss implications by considering when additive decision rules are dysfunctional, the interpretation of overconfidence based on contest-entry behavior, and the use of aids to help people make better decisions.


Single kinesin molecules crossbridge microtubules in vitro.
Kinesin is a cytoplasmic motor protein that moves along microtubules and can induce microtubule bundling and sliding in vitro. To determine how kinesin mediates microtubule interactions, we determined the shapes and mass distributions of squid brain kinesin, taxol-stabilized microtubules (squid and bovine), and adenosine 5'-[beta, gamma-imido]triphosphate-stabilized kinesin-microtubule complexes by high-resolution metal replication and by low-temperature, low-dose dark-field scanning transmission electron microscopy of unfixed, directly frozen preparations. Mass mapping by electron microscopy revealed kinesins loosely attached to the carbon support as asymmetrical dumbbell-shaped molecules, 40-52 nm long, with a mass of 379 +/- 15 kDa. The mass distribution and shape of these molecules suggest that these images represent kinesin in a shortened conformation. Kinesin-microtubule complexes were organized as bundles of linearly arrayed microtubules, stitched together at irregular intervals by cross-bridges typically < or = 25 nm long. The crossbridges had a mass of 360 +/- 15 kDa, consistent with one kinesin per crossbridge. These results suggest that kinesin has a second microtubule binding site in addition to the known site on the motor domain of the heavy chain; this second site may be located near the C terminus of the heavy chains or on the associated light chains. Thus, kinesin could play a role in either crosslinking or sliding microtubules.


Tele-consultations in the wake of COVID-19 - Suggested guidelines for clinical ophthalmology.
While telemedicine has been around for a few decades, it has taken great importance and prominence in recent times. With the fear of the virus being transmitted, patients and physicians across specialties are using consultation via a telephone call or video from the safety of their homes. Though tele-ophthalmology has been popular for screening, there are no clear guidelines on how to comprehensively manage patients seeking advice and treatment for a particular eye condition. Some major barriers to diagnosis and management are compromised detailed examination, no measurement of the visual acuity or intraocular pressure and a retinal evaluation not being feasible. Despite these limitations, we do need to help those patients who need immediate care or attention. Hence, this article has put together some guidelines to follow during such consultations. They are important and timely due to the medicolegal and financial implications.


The influence of social networks and social support on violence by persons with serious mental illness.
The authors examined the relationship between violent acts and threats by persons with serious mental illness, the size and composition of their social networks, and characteristics of the social support they received. A group of 169 respondents with serious mental illness and 59 of their significant others were interviewed using structured and semi-structured protocols to elicit data on demographic characteristics, clinical characteristics, characteristics of respondents' social networks and of the social support they received, and perceptions of threat within the social network. Data on acts and threats of violence by respondents over an 18-month period were collected from self-reports by respondents and significant others and from hospital and court records. Fifty-six respondents either threatened violence or committed a violent act during the study period. Respondents with a diagnosis of schizophrenia were more likely to commit violent acts but were not more likely to threaten violence than were respondents with other diagnoses. Respondents in larger networks, those with networks composed primarily of relatives, and those who lived with unrelated persons were more likely to threaten violence. Financial dependence on family was associated with more violent threats and acts. Respondents who perceived hostility from others were more likely to engage in violent threats and acts, and those with confused thinking were less likely to act or threaten violence. More than half of the targets of violence were respondents' relatives, particularly mothers living with a respondent. Respondents who were violent perceived their significant others as threatening but did not perceive themselves as being threatening in return. The interpersonal and social contexts of respondents and their perceptions of these contexts are important considerations in assessing risk for violence by persons with mental illness. Mothers who live with an adult offspring with schizophrenia may be at increased risk for being a target of violence. Violence by persons with psychiatric disorders may be linked to their perceptions and experience of being threatened by others.


Is Retention of the Acetabular Component at Revision Surgery a Long-Term Solution?
Acetabular retention in revision total hip arthroplasty (THA) may be advantageous, yet long-term survival data is limited. Thus, we investigated long-term survivorship of retained acetabular components in revision THA with analysis of rerevision rate, instability risk, and clinical outcomes. We reviewed 98 hips with polyethylene wear and/or osteolysis that were revised with retained acetabular components. Acetabular inclination and anteversion were measured from prerevision radiographs. A retrospective chart review was performed, collecting outcomes of interest including Harris hip score, instability events, and rerevision surgery. Kaplan-Meier analysis was used to calculate the risk of revision over time. Predictors of survival including acetabular component position were analyzed by multiple logistic regression. Average follow-up was 13 years (range, 5-24). Survivorship rates at 5, 10, 15, and 20 years were 89.7%, 81.6%, 70.8%, and 63.8%, respectively. There was improvement in average Harris hip score (61 to 76, P < .0001). There was a 9% rate of dislocation, and 6 hips (6%) were rerevised for recurrent instability. Overall, there were 23 (23%) rerevisions at an average of 6.1 years with the most common reasons being instability (6%) and aseptic loosening (6%). Use of conventional polyethylene was the only identified independent predictor of rerevision (P = .025). Retention of a well-fixed acetabular component in revision THA provides acceptable long-term outcomes with a 15-year survivorship of 71%. Instability and aseptic loosening were the most common reasons for rerevision. Surgeons may consider retaining the acetabular component at revision surgery if the implant is well-fixed and well-positioned.


Ethanol fraction of Aralia elata Seemann enhances antioxidant activity and lowers serum lipids in rats when administered with benzo(a)pyrene.
Aralia elata Seemann is an edible mountain vegetable in Korea containing saponin, alkaloid, palmitic acid, linoleic acid, methyl eicosanoate and hexacosol, and is known to manifest an effect on cardiac infarction, gastric ulcer, colitis, and enervation. This study has examined the effects of Aralia elata Seemann ethanol extract on antioxidant enzyme systems and lipid metabolism in rats along with benzo(a)pyrene (B(a)P) administration. Rats were divided into four groups: control (C), an extract fed group (CE), a B(a)P fed group (CB), and a B(a)P and extract fed group (CBE). The ethanol extracts of Aralia elata Seemann (50 mg/kg body weight) were fed to the rats for 4 weeks by stomach tubing. Extract administration increased the antioxidant activities of glutathione sulfur transferase (GST). Total superoxide dismutase (SOD) and Cu,Zn-SOD activities were stimulated. Catalase activities were increased by 50% with extract feeding. Cu,Zn-SOD was greatly enhanced from 0.10 unit to 0.18 unit and catalase activity also was increased. Serum alpha-tocopherol was markedly increased by the extracts. The ethanol fraction of Aralia elata Seemann decreased total serum cholesterol. However, serum HDL-cholesterol was increased by 35% (p<0.05). The results indicate that Aralia elata Seemann exerts antioxidant and strong hypocholesterolemic and hypolipidemic effects in vivo with the administration of B(a)P.


Evaluation of the nonorganic hearing loss suspect.
To examine the utility of distortion-product otoacoustic emissions (DPOAEs) in the assessment of the nonorganic suspect because DPOAE analysis constitutes an objective test of hair-cell function that yields audiometriclike data. Retrospective study of clinical findings. Audiology outpatient clinic of our university's medical center. The study cohort comprised 30 patients who presented with a profile of suspicion for nonorganic hearing loss. Most cases were found, with the aid of DPOAE testing, to be nonorganic or to have nonorganic overlays to organic hearing loss. Interventions were diagnostic only. Observed audiometric findings and changes thereof. Statistically significant decreases in thresholds occurred in subgroups of those cases deemed to be truly nonorganic in origin. Especially considering test efficiency, the results support the inclusion of DPOAE analysis in the diagnostic management of the suspect-nonorganic patient.


Phototoxic lysis of erythrocytes from humans is reduced after oral intake of ascorbic acid and d-alpha-tocopherol.
Ultraviolet (UV) radiation causes hemolysis of human erythrocytes in the presence of photosensitizers. This can be used as an in vitro model for evaluating photosensitizing properties of substances. Antioxidants such as ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E) have been found to be photoprotective in such test systems. We assessed the effect of combined systemic intake of both ascorbic acid and d-alpha-tocopherol by human volunteers on phototoxic in vitro lysis of their erythrocytes. In a double-blind placebo-controlled study, 10 subjects took daily 2 g ascorbic acid combined with 1000 IU d-alpha-tocopherol, and 10 took a placebo. Blood was taken before and after 7 days of treatment, erythrocytes were prepared and then incubated with 10(-3) mol/l fenofibrate, a photosensitizer acting in the UVA and UVB region. The suspensions were exposed to radiation rich in UVA (up to 40 J/cm2 UVA) or to radiation rich in UVB (up to 1.6 J/cm2). Photohemolysis of the samples was calculated as a percentage of complete hemolysis. At the end of the treatment phase, in the placebo group photohemolysis was not significantly reduced compared with the initial values at all irradiation doses except for 1.6 J/cm2 UVB (96% vs 79%; P < 0.01). In the group taking vitamins, photohemolysis was significantly reduced at nearly all UV doses, most impressively after moderate UVA irradiation (20 J/cm2 UVA: 86.5% vs 14.5%; P < 0.01). It is concluded that the results of the photohemolysis test are influenced by the antioxidative status of the cell donor and that ascorbic acid and d-alpha-tocopherol also may protect against phototoxic damage in vivo.


Challenges in assessing intent to die: can suicide attempters be trusted?
Assessing a person's intent to die in a suicide attempt is crucial for risk assessment and research, yet suicidal intent is notoriously difficult to measure. People who intended to die when they hurt themselves may deny it, and others may feign intent for secondary gain. Additionally, ambivalence, memory gaps, impulsivity, and fluidity of intent can hinder accurate assessment of intent. Circumstantial evidence, such as a suicide note, may illuminate true intentions but also has substantial limitations. This article summarizes disparate challenges to the measurement of suicidal intent; describes strengths and weaknesses of circumstantial indicators; reviews evidence from studies using the Suicide Intent Scale to show that subjective and circumstantial indicators do not strongly correlate with each other; and concludes with a call to place more trust in individuals whose disclosures of suicidal intent are questionable, even if the possibility for manipulation exists.


Characterization of two VQIXXK motifs for tau fibrillization in vitro.
Tau proteins are building blocks of the filaments that form neurofibrillary tangles of Alzheimer's disease (AD) and related neurodegenerative tauopathies. It was recently reported that two VQIXXK motifs in the microtubule (MT) binding region, named PHF6 and PHF6*, are responsible for tau fibrillization. However, the exact role each of these motifs plays in this process has not been analyzed in detail. Using a recombinant human tau fragment containing only the four MT-binding repeats (K18), we show that deletion of either PHF6 or PHF6* affected tau assembly but only PHF6 is essential for filament formation, suggesting a critical role of this motif. To determine the amino acid residues within PHF6 that are required for tau fibrillization, a series of deletion and mutation constructs targeting this motif were generated. Deletion of VQI in either PHF6 or PHF6* lessened but did not eliminate K18 fibrillization. However, removal of the single K311 residue from PHF6 completely abrogated the fibril formation of K18. K311D mutation of K18 inhibited tau filament formation, while K311A and K311R mutations had no effect. These data imply that charge change at position 311 is important in tau fibril formation. A similar requirement of nonnegative charge at this position for fibrillization was observed with the full-length human tau isoform (T40), and data from these studies indicate that the formation of fibrils by T40K311D and T40K311P mutants is repressed at the nucleation phase. These findings provide important insights into the mechanisms of tau fibrillization and suggest targets for AD drug discovery to ameliorate neurodegeneration mediated by filamentous tau pathologies.


Beyond knowledge, toward linguistic competency: an experiential curriculum.
Training is essential for future health care providers to effectively communicate with limited English proficient (LEP) patients during interpreted encounters. Our aim is to describe an innovative skill-based medical school linguistic competency curriculum and its impact on knowledge and skills. At Stanford University School of Medicine, we incorporated a linguistic competency curriculum into a 2-year Practice of Medicine preclinical doctoring course and pediatrics clerkship over three cohorts. First year students participated in extensive interpreter-related training including: a knowledge-based online module, interactive role-play exercises, and didactic skill-building sessions. Students in the pediatrics clerkship participated in interpreted training exercises with facilitated feedback. Knowledge and skills were evaluated in the first and fourth years. First year students' knowledge scores increased (pre-test = 0.62, post-test = 0.89, P < 0.001), and they demonstrated good skill attainment during an end-year performance assessment. One cohort of students participated in the entire curriculum and maintained performance into the fourth year. Our curriculum increased knowledge and led to skill attainment, each of which showed good durability for a cohort of students evaluated 3 years later. With a growing LEP population, these skills are essential to foster in future health care providers to effectively communicate with LEP patients and reduce health disparities.


Comparative transcriptome and proteome analyses of the longissimus dorsi muscle for explaining the difference between donkey meat and other meats.
Domestic donkeys (Equus asinus) have been maintained mainly for service purposes in the past. Nowadays, there is an increasing interest in donkey milk and meat production in several countries, including China. Donkey meat is highly consumed because of its nutritional value and unique flavor. However, genomic studies on donkey meat are limited. Therefore, in this study, we aimed to examine the molecular difference of longissimus dorsi muscles of donkey, cow, and goat. RNA sequencing and Proteome sequencing technology were used to analyze the transcriptome and proteome of the longissimus dorsi muscle of donkey, cow, and goat. A total of 1338 and 1780 differentially expressed genes (DEGs) were identified in donkey meat compared with that in cow and goat meat, respectively. Most of the DEGs were involved in biological processes, including small GTPase-mediated signal transduction, protein ubiquitination, protein glycosylation, and MAP kinase tyrosine/serine/threonine phosphatase activity. Additionally, 764 and 1024 differentially expressed proteins (DEPs) were identified in cow vs. donkey, and goat vs. donkey, respectively; these DEPs were mainly involved in metabolism. Genetic variation and regulatory factors can combine as a database to provide more valuable molecular information for further analysis.


Cytokines in neuroblastoma: from pathogenesis to treatment.
Cytokines released by cancer cells or by cells of the tumor microenvironment stimulate angiogenesis, act as autocrine or paracrine growth factors for malignant cells, promote tumor cell migration and metastasis or create an immunosuppressive microenvironment. These tumor-promoting effects of cytokines also apply to neuroblastoma (NB), a pediatric neuroectodermal malignancy with frequent metastatic presentation at diagnosis and poor prognosis. IL-6 and VEGF are the best characterized cytokines that stimulated tumor growth and metastasis, while others such as IFN-γ can exert anti-NB activity by inducing tumor cell apoptosis and inhibiting angiogenesis. On the other hand, cytokines are part of the anti-NB therapeutic armamentarium, as exemplified by IL-2 and granulocyte-macrophage colony stimulating factor that potentiate the activity of anti-NB antibodies. These recent results raise hope for more efficacious treatment of this ominous pediatric malignancy.


Hepatocellular carcinomas show abnormal expression of fibronectin protein.
Fibronectin plays an important role in cell-to-cell adhesion, cell migration, and cell signaling. In the liver, fibronectin expression has been studied primarily as a component of the extracellular matrix, but little information is available on the expression of fibronectin protein in the neoplastic cells of hepatocellular carcinomas (HCCs). Twenty-four surgically resected HCCs were immunostained with fibronectin. Tumor and normal liver tissues were concurrently analyzed in all cases, and expression in the tumor was evaluated in comparison to the nonneoplastic liver. The average age at resection was 54 +/- 18 years for the 18 men and 6 women. Twenty-one of the cases were classic HCCs including 6 cases that were well differentiated, 12 cases moderately differentiated, and 3 cases poorly differentiated. The remaining 3 cases were moderately differentiated fibrolamellar carcinomas. In the normal liver, fibronectin labeled the sinusoids and weakly to moderately stained the cytoplasm of hepatocytes. In HCCs, 15/24 showed overexpression of fibronectin in the cytoplasm, 8/24 showed no change from the nonneoplastic liver, and one case showed decreased cytoplasmic staining. In addition, an abnormal membranous staining pattern was noted in 16/24 HCCs. In contrast to the HCCs, none of the three fibrolamellar carcinomas showed increased cytoplasmic or membranous staining. Excluding fibrolamellar carcinoma, increased cytoplasmic staining and/or an abnormal membranous staining was noted in 19/21 (90%) of HCCs. Fibronectin shows abnormal cytoplasmic and/or membranous staining in the majority of HCCs. The implications of fibronectin overexpression are uncertain but may reflect a critical step in tumor genesis.


IL-8 and IDO expression by human gingival fibroblasts via TLRs.
Human gingival fibroblasts (HGFs), a predominant cell type in tooth-supporting structure, are presently recognized for their active role in the innate immune response. They produce a variety of inflammatory cytokines in response to microbial components such as LPS from the key periodontal pathogen, Porphyromonas gingivalis. In this study, we demonstrated that HGFs expressed mRNA of TLRs 1, 2, 3, 4, 5, 6, and 9, but not TLRs 7, 8, and 10. Stimulation of HGFs with highly purified TLR2 ligand (P. gingivalis LPS), TLR3 ligand (poly(I:C)), TLR4 ligand (Escherichia coli LPS), and TLR5 ligand (Salmonella typhimurium flagellin) led to expression of IL-8 and IDO. A potent TLR 9 ligand, CpG oligodeoxynucleotide 2006 had no effect, although HGFs showed a detectable TLR9 mRNA expression. No significant enhancement on IL-8 or IDO expression was observed when HGFs were stimulated with various combinations of TLR ligands. Surprisingly, the TLR9 ligand CpG oligodeoxynucleotide 2006 was able to specifically inhibit poly(I:C)-induced IL-8 and IDO expression. TNF-alpha enhanced TLR ligand-induced IL-8 production in HGFs, whereas IFN-gamma enhanced TLR ligand-induced IDO expression. HGF production of IDO in response to P. gingivalis LPS, IFN-gamma, or the two in combination inhibited T cell proliferation in MLRs. The observed T cell inhibition could be reversed by addition of either 1-methyl-dl-tryptophan or l-tryptophan. Our results suggest an important role of HGFs not only in orchestrating the innate immune response, but also in dampening potentially harmful hyperactive inflammation in periodontal tissue.


Effect of macromolecular synthesis and lytic capacity on surface growth of Streptococcus faecalis.
Exposure of exponential-phase cultures of Streptococcus faecalis to any of three inhibitors of protein synthesis was accompanied by an increase in the average distance that the cross wall extended into the cytoplasm. This resulted in: (i) an increase in the average surface area of the cross wall (Sa) and (ii) septation occurring in the envelope growth sites that were much smaller than the controls. However, although at the concentrations used, all three antibiotics inhibited protein synthesis and autolytic capacity to the same extent and with the same kinetics, cells treated with these agents showed large differences in the rate at which Sa values increased above those of the untreated cells. The largest increases in Sa were observed in cells that synthesized the least amount of cytoplasmic macromolecules (deoxyribonucleic acid, plus ribonucleic acid, plus protein). The observations were interpreted in terms of a model in which a decreased lytic capacity reduces the rate of splitting of the nascent cross wall into two layers of peripheral wall, preferentially using wall precursors to close open cross walls. However, the extent to which centripetal growth occurs would be inversely related to the rate at which cytoplasmic macromolecules are synthesized. In contrast, inhibition of deoxyribonucleic acid synthesis was accompanied by decreased extension of the leading edge of the cross wall into the cytoplasm, thus antagonizing septation. These findings are discussed in relation to the normal cell division cycle of S. faecalis.


A genetic electrophoretic variant of human hair alpha polypeptides.
The structural proteins of hair were solubilized by reduction of disulfide bonds in 6 M urea at alkaline pH. Following conversion of the proteins to the S-carboxy-methyl derivatives, disc electrophoresis was done in 6 M urea at pH 8.3. In about 5% of the individuals studied, a variation in the normal electrophoretic pattern was observed, and this was true of hair from different body sites. An autosomal dominant mode of inheritance was found in the four families investigated. The variant pattern was not associated with any detectable change in the color, shape, stree-strain characteristics, X-ray diffraction pattern, or amino acid composition of the hair. A similar variant pattern was also observed in nail. The most likely hypothesis is that there is a polymorphism of one of the alpha polypeptides, although a mutation of a rate-determining gene cannot be excluded.


Psychological impact of violence on male nurses in forensic units in Gauteng, South Africa.
Male psychiatric nurses are pivotal in providing treatment, care and rehabilitation to state patients admitted to forensic units. The nature of patients admitted in forensic units increase the likelihood violence for male psychiatric nurses. Substantial evidence suggests that a high incidence of violence in such units is linked to lack of security personnel amongst other factors, adding to the strain. Fewer studies adequately explored the psychological impact thereof specifically on male psychiatric nurses. To explore the psychological impact of violence on male nurses working in forensic units in Gauteng, South Africa, and the strategies used to deal with the impact of exposure to violence. The study was conducted at a mental health institution in the west of Tshwane Gauteng, South Africa. An exploratory, qualitative research design was used. In-depth interviews were used to collect data from 11 male psychiatric nurses. Data were analysed using thematic analysis. Two main overarching themes emerged: (1) Traumatic experience and (2) Survival strategies to deal with the experience. The results suggest that exposure to violence has a debilitating psychological effect on male nurses, prompting them to utilise various ways to cope with the experiences. Psychological support and skills development could benefit male psychiatric nurses to manage the impact of violence adequately. Further research is recommended to explore the strategies to support male psychiatric nurses working in forensic units. The study findings may be used to improve the psychological well-being of male psychiatric nurses working in forensic units in South Africa.


Three-dimensional CT demonstration of intrahepatic portosystemic venous shunt draining into the inferior vena cava.
An unusual form of intrahepatic portosystemic venous shunt draining into the inferior vena cava was demonstrated using three-dimensional images reconstructed from spiral CT during arterial portography, colour Doppler ultrasonography with flow velocity measurement, and digital subtraction portovenography. The utilization of modern radiological techniques in evaluating intrahepatic portosystemic venous shunts is discussed.


Evaluation of the economic benefits, administration times, and patient preferences associated with the use of biotechnological drugs administered subcutaneously and intravenously in patients with cancer: a systematic review.
Cancer imposes a high economic burden with medical care and medication costs. We evaluate the costs, the use of resources, the administration time, and the patient preferences associated with the use of biotechnological drugs in SC and IV presentations. A systematic literature search was conducted in PubMed, Embase, and seven additional databases. The search was carried out in September 2021 and included only studies directly comparing SC and IV presentations. Evidence was synthesized narratively. 34 references were included, which only analyzed bortezomib, daratumumab, rituximab, and trastuzumab. Reduction in preparation costs of SC compared to IV presentations ranged from 6.6% to 50.1%, and in administration costs from 4.5% to 95.3%. SC administration of rituximab and trastuzumab resulted in less productivity loss. More than 68% of patients reported greater satisfaction with the SC route. A reduction of time in the infusion chair, lower costs of resources for preparation, and health personnel for the administration process were identified with SC administration. The use of SC daratumumab, rituximab, and trastuzumab in patients with cancer reduces direct and indirect costs and adverse events compared to IV use. Patients prefer the SC administration, perceiving more comfort, and less pain at the administration site.


Circumstellar and interstellar synthesis of organic molecules.
We review the formation and evolution of complex circumstellar and interstellar molecules. A number of promising chemical routes are discussed which may lead to the formation of polycyclic aromatic hydrocarbon molecules, fullerenes, and unsaturated hydrocarbon chains in the outflows from stars. Some of the problems with these chemical schemes are pointed out as well. We also review the role of grains in the formation of complex molecules in interstellar molecular clouds. This starts with the formation of simple molecules in an ice grain mantle. UV photolysis and/or thermal polymerization can convert some of these simple molecules into more complex polymeric structures. Some of these species may be released to the gas phase, particularly in the warm regions around newly formed stars. Methanol and formaldehyde seem to play an important role in this drive towards molecular complexity and their chemistry is traced in some detail.


Carbon nanotube coated paper sensor for damage diagnosis.
A carbon nanotube coated paper sensor has been developed for the detection of damages in structural components. Electrical resistance tomography is used to measure changes in electrical potential at various locations induced by applying a small electrical current to the sample. The spatial locations and magnitudes of multiple damages are predicted accurately with a sensitivity of 73 ppm in sensing area. The detection limit of the sensor is estimated to be 29 ppm in sensing area, which is at least 30 times better in sensitivity than previous results (0.1-0.65%) in the literature.


A new site-directed transgenic rheumatoid factor mouse model demonstrates extrafollicular class switch and plasmablast formation.
The AM14 rheumatoid factor (RF) transgenic (Tg) mouse has been valuable for studying how self-reactive B cells are regulated beyond central tolerance, because they remain ignorant in normal mice. AM14 B-cell activation can be studied on autoimmune-prone strains or by inducing activation with IgG2a anti-chromatin antibodies (Abs). Despite the utility of conventional Ig-Tg mice, site-directed Ig-Tg (sd-Tg) mice provide a more physiological model for B-cell responses, allowing class switch and somatic hypermutation. We report here the creation of an AM14 sd-Tg mouse and describe its phenotype on both normal and autoimmune-prone backgrounds. AM14 sd-Tg B cells develop normally but remain unactivated in the BALB/c background, even after significant aging. In contrast, in the autoimmune-prone strain MRL/lpr, AM14 sd-Tg B cells become activated and secrete large amounts of IgG RF Ab into the serum. Class-switched Ab-forming cells were found in the spleen and bone marrow. IgG RF plasmablasts were also observed in extrafollicular clusters in the spleens of aged AM14 sd-Tg MRL/lpr mice. Class switch and Ab secretion were observed additionally in AM14 sd-Tg BALB/c B cells activated in vivo using IgG2a anti-chromatin Abs. Development of IgG auto-Abs is a hallmark of severe autoimmunity and is related to pathogenesis. Using the AM14 sd-Tg, we now show that switched auto-Ab-forming cells develop robustly outside germinal centers, further confirming the extrafollicular expression of activation induced cytidine deaminase (AID). This model will allow more physiological studies of B-cell biology in the future, including memory responses marked by class switch.


[Modified method of blood perfusion via xenospleen in patients with peritonitis].
The authors compare the therapeutic efficacies of blood perfusion via porcine spleen and of discrete plasmapheresis followed by perfusion of formed elements of the blood via the porcine spleen by their own accord, included in the postoperative multiple-modality treatment of patients with the toxic and terminal phases of diffuse peritonitis. Discrete plasmapheresis followed by perfusion of formed elements of the blood via the xenospleen by their own accord yielded a more marked detoxifying and immunomodulating effect than hemosplenosorption, was simple to perform and associated with no complications. Use of this method in patients with diffuse peritonitis improved the efficacy of surgical treatment at the expense of reduction in the incidence of the postoperative complications and decreased mortality rates.


On the 'lost' crops of the neolithic Near East.
The claim that the 'classic' eight 'founder crop' package (einkorn wheat, emmer wheat, barley, lentil, pea, chickpea, bitter vetch, and flax) underlying the emergence of agriculture in the Near East is a relic of a larger number of domesticated species is addressed. The 'lost' crops concept relies on the idea that additional taxa were at certain points in time and in certain locations genuine crops, which were later abandoned. The issue is highly relevant to the debate concerning mono- versus polyphyletic domestication, because if there were numerous 'false starts' that were subsequently lost, this implies that plant domestication occurred over a protracted time period, and across a wide geographic range. Different criteria were used for declaring those taxa as 'lost' crops, including, but not limited to (i) identification in archaeobotanical assemblages of grains from species which are not known as crops at present; (ii) identification of such grains in what is interpreted to have been Neolithic storage facilities; and (iii) recent botanical observations on populations of crop wild relatives in disturbed habitats. The evidence for four presumed 'lost' crops (wild oat, rambling vetch, rye, and wild black lentil) and the broad bean is evaluated, and discussed in light of data on Croatian and Israeli wild pea, and Moroccan wild lentil in disturbed habitats. Based on present knowledge, the broad bean might emerge as a founder crop (without an identified wild progenitor). The same may hold true for rye, which was never lost since its adoption in the Pre-Pottery Neolithic B period in Anatolia. In the remaining three cases, there are alternative, more likely, explanations for the archaeological finds or the recent botanical observations rather than 'lost' domestication episodes.


Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds.
Allium vegetables, such as garlic, have been used for medicinal purposes throughout the recorded history. The known health benefits of Allium vegetables constituents include cardiovascular effects, improvement of the immune function, lowering of blood glucose level, radioprotection, protection against microbial infections, and anti-cancer effects. Initial evidence for the anti-cancer effect of Allium vegetables was provided by population-based case-control studies. Subsequent laboratory studies showed that the Allium vegetable constituents, such as diallyl disulfide, S-allylcysteine, and ajoene can not only offer protection against chemically induced cancer in animal models by altering carcinogen metabolism, but also suppress growth of cancer cells in culture and in vivo by causing cell cycle arrest and apoptosis induction. Suppression of angiogenesis and experimental metastasis by Allium constituents has also been reported. Defining the mechanism by which sulfur compounds derived from Allium vegetables inhibit cancer cell growth has been the topic of intense research in the last two decades. Some Allium vegetable constituents have also entered clinical trials to assess their safety and anti-cancer efficacy. This article summarizes preclinical and limited clinical data to warrant further clinical evaluation of Allium vegetable constituents for prevention and therapy of human cancers.


Acyl-coenzyme A:cholesterol acyltransferase-2 (ACAT-2) is responsible for elevated intestinal ACAT activity in diabetic rats.
Diabetes-induced dyslipidemia is seen in streptozotocin-induced diabetic rats. This is caused, in part, by elevated intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity. Because two ACAT isozymes (ACAT-1 and ACAT-2) were identified, in the present study we determined which ACAT isozyme was involved in the elevated intestinal ACAT activity in diabetic rats. We cloned a full-length cDNA of rat ACAT-2. Its overexpression in ACAT-deficient AC29 cells demonstrated that the ACAT activity is derived from the cloned cDNA, and a 45-kDa protein of rat ACAT-2 cross-reacts with an anti-human ACAT-2 antibody. The tissue distribution of rat ACAT-2 mRNA revealed its restricted expression to liver and small intestine. Immunohistochemical analyses using an anti-human ACAT-2 antibody demonstrated that ACAT-2 is localized in villus-crypt axis of rat small intestine. The intestinal ACAT activity in diabetic rats was significantly immunodepleted by an anti-ACAT-2 antibody but not by an anti-ACAT-1 antibody. Finally, intestinal ACAT-2 in diabetic rats significantly increased at both protein and mRNA levels as compared with that in control rats. Our data demonstrate that ACAT-2 isozyme is responsible for the increased intestinal ACAT activity of diabetic rats, suggesting an important role of ACAT-2 for dyslipidemia in diabetic patients. Diabetic rats exhibit dyslipidemia caused, in part, by elevated intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity. We determined which ACAT isozyme (ACAT-1 or ACAT-2) was involved in the elevated intestinal ACAT activity in diabetic rats. We demonstrated an important role of ACAT-2, implicating its involvement in dyslipidemia in diabetic patients.


Comparative Proteomics of Tumor and Paired Normal Breast Tissue Highlights Potential Biomarkers in Breast Cancer.
Breast cancer is the most common type of cancer among women worldwide, and about 57,000 new cases are expected for the Brazilian population in 2015. Elucidation of protein expression and modification is essential for the biological understanding, early diagnosis and therapeutics of breast cancer. The main objectives of the study are comparison between the proteome of tumor and paired non-tumor breast cancer tissues, describing all identified proteins, highlighting the ones most differentially expressed and comparing the data with existing literature. The five paired samples from patients with invasive ductal carcinoma were analyzed by 2-DE and MS. We collected 161 identified spots corresponding to 110 distinct proteins. Forty-three differentially-expressed spots were common to at least two samples, and the ten proteins with the highest-fold changes were CASPE, ENOG, TPM1, CAPG, VIME, TPM3, TRFE, PDIA6, WDR61 and PDIA3. Metabolic enzymes and proteins with binding functions were the most representative functional classes of proteins with increased and decreased expression in tumor tissue respectively. Taking the fold change as a parameter, we point to future targets to be studied by functional methods in a search for biomarkers for initiation and progress of breast cancer.


Ice and water droplets on graphite: a comparison of quantum and classical simulations.
Ice and water droplets on graphite have been studied by quantum path integral and classical molecular dynamics simulations. The point-charge q-TIP4P/F potential was used to model the interaction between flexible water molecules, while the water-graphite interaction was described by a Lennard-Jones potential previously used to reproduce the macroscopic contact angle of water droplets on graphite. Several energetic and structural properties of water droplets with sizes between 10(2) and 10(3) molecules were analyzed in a temperature interval of 50-350 K. The vibrational density of states of crystalline and amorphous ice drops was correlated to the one of ice Ih to assess the influence of the droplet interface and molecular disorder on the vibrational properties. The average distance of covalent OH bonds is found 0.01 Å larger in the quantum limit than in the classical one. The OO distances are elongated by 0.03 Å in the quantum simulations at 50 K. Bond distance fluctuations are large as a consequence of the zero-point vibrations. The analysis of the H-bond network shows that the liquid droplet is more structured in the classical limit than in the quantum case. The average kinetic and potential energy of the ice and water droplets on graphite has been compared with the values of ice Ih and liquid water as a function of temperature. The droplet kinetic energy shows a temperature dependence similar to the one of liquid water, without apparent discontinuity at temperatures where the droplet is solid. However, the droplet potential energy becomes significantly larger than the one of ice or water at the same temperature. In the quantum limit, the ice droplet is more expanded than in a classical description. Liquid droplets display identical density profiles and liquid-vapor interfaces in the quantum and classical limits. The value of the contact angle is not influenced by quantum effects. Contact angles of droplets decrease as the size of the water droplet increases which implies a positive sign of the line tension of the droplet.


Degradation of geosmin-like compounds by selected species of gram-positive bacteria.
Biodegradation of geosmin produced by Streptomyces halstedii (A-1 strain) was investigated using seven Gram-positive bacteria. Bacterial action on the A-1 extract was followed at 15, 45 and 120 min. Bacillus cereus ssp. thuringiensis HD-1, B. cereus 3711 and B. cereus ssp. mycoides 4379 showed no effect. However, Arthrobacter atrocyaneus, Arth. globiformis, Chlorophenolicus N-1053 and Rhodococcus maris caused a colour change from blue to yellow (positive reaction). These data suggest that geosmin can be degraded by specific species of Gram-positive bacteria. Biodegradation of geosmin, which causes bad odour in drinking water, can be used as a new technology in water treatment.


When Asian immigrant women speak: from mental health to strategies of being.
Immigrant women from 5 ethnic-cultural communities (Korean, Hong Kong Chinese, Mainland Chinese, Taiwanese, and Vietnamese) in Toronto, Ontario, Canada participated in a focus group study (13 focus groups of 102 participants) of Asian immigrant women's conceptions of mental health. Their responses challenge the predominant conceptualizations of mental health in North America, the popular characterization of Asian culture as collectivistic, and the stereotypic image of Asian women as defining themselves in family relations. In trying to live a life they desire and to quest for a better state of well-being, these women have asserted their agency to articulate multiple strategies of being.


Influencing factors of life satisfaction among medical staff of rehabilitation departments based on a structural equation model.
Life satisfaction (LS) exhibited gender differences and was associated with age, income, and negative emotions. There is no research on the relationship between professional values and LS, although professional values are essential for medical staff and correlate with negative emotions. This study aimed to explore the relationship between professional values and LS, the action mechanism of influencing factors of LS, and gender differences among medical staff of rehabilitation departments in China. A total of 284 participants (108 men and 176 women) completed the questionnaires. Data were analyzed using SPSS19.0 and Amos21.0. Age, length of service, and anxiety differed significantly between genders. Professional values had a direct effect on LS and an indirect effect on LS via anxiety and depression. Therefore, enhancing professional values and reducing anxiety and depression could increase the medical staff's LS. Moreover, the LS of female medical staff improved with age.


A randomized crossover trial on the effect of compression stockings on nausea and vomiting in early pregnancy.
This study aimed to assess the impact of wearing compression stockings on women's quality of life (QoL) associated with nausea and vomiting in early pregnancy (NVP). In this randomized, open, single-center, crossover study, 74 women were assigned 1:1 to 2 weeks with compression stockings followed by 2 weeks without or vice versa. The main outcomes were NVP-associated QoL, leg-related QoL, and dizziness, as assessed by the Nausea and Vomiting in Pregnancy Quality of Life (NVPQOL) questionnaire, Chronic Venous Disease Quality of Life (CIVIQ) questionnaire, and questions on dizziness at baseline and after each 2-week period, respectively. Daily NVP was assessed using the modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) questionnaire. Data were analyzed using Pearson's chi-square and independent t-tests. Fifty-eight women completed the study. QoL scores improved with compression treatment; changes in mean total scores were as follows: NVPQOL, -36.7 with compression vs -21.7 without (P<0.0001); and CIVIQ, -4.5 with compression vs +1.4 without (P=0.001). Mean dizziness scores were -3.2 with compression vs -0.4 without (P<0.0001). PUQE mean total score (standard deviation) was 4.9 (2.3) with compression vs 5.5 (2.2) without (P=0.042). Wearing of compression stockings in early pregnancy may improve nausea and vomiting-associated symptoms in addition to improving QoL factors.


Prestrain and cholinergic receptor-dependent differential recruitment of mechanosensitive energy loss and energy release elements in airway smooth muscle.
We tested the hypothesis that oscillatory airway smooth muscle (ASM) mechanics is governed by mechanosensitive energy loss and energy release elements that can be recruited by prestrain and cholinergic stimulation. We measured mechanical energy loss and mechanical energy release in unstimulated and carbachol-stimulated bovine ASM held at prestrains ranging from 0.3 to 1.0 Lo (reference length) and subjected to sinusoidal length oscillation at 1 hz with oscillatory strain amplitudes ranging from 0.1 to 1.5% Lo. We found that oscillatory ASM mechanics during sinusoidal length oscillation is governed predominantly by one class of nonlinear mechanosensitive energy loss element and one class of nonlinear mechanosensitive energy release element with differential mechanosensitivities to oscillatory strain amplitude. The greater mechanosensitivity of the energy loss element than energy release element may explain the bronchodilatory effect of deep inspiration. Prestrain, an important determinant of ASM responsiveness, differentially increased energy loss and energy release in unstimulated and carbachol-stimulated ASM. Cholinergic stimulation, an important cause of bronchoconstriction and airway inflammation, also differentially increased energy loss and energy release. When prestrain and cholinergic stimulation were combined, we found that prestrain and cholinergic stimulation synergistically increased energy loss and energy release by ASM. The relationship between recruitment of energy loss elements and recruitment of energy release elements was nonlinear, suggesting that energy loss and energy release elements are not coupled in ASM cells. These findings imply that large lung volume and cholinergic ASM activation would synergistically increase mechanical energy expenditure during inspiration and mechanical recoil of ASM during expiration. NEW & NOTEWORTHY We report for the first time that oscillatory airway smooth muscle mechanics is governed predominantly by one class of nonlinear mechanosensitive energy loss element and one class of nonlinear mechanosensitive energy release element with differential mechanosensitivities to oscillatory strain amplitude. Prestrain and cholinergic stimulation synergistically and differentially recruit energy loss and energy release elements. The greater mechanosensitivity of the energy loss element than the energy release element may explain the bronchodilatory effect of deep inspiration.


Arsenic Methylation Capacity and Metabolic Syndrome in the 2013-2014 U.S. National Health and Nutrition Examination Survey (NHANES).
Arsenic methylation capacity is associated with metabolic syndrome and its components among highly exposed populations. However, this association has not been investigated in low to moderately exposed populations. Therefore, we investigated arsenic methylation capacity in relation to the clinical diagnosis of metabolic syndrome in a low arsenic exposure population. Additionally, we compared arsenic methylation patterns present in our sample to those of more highly exposed populations. Using logistic regression models adjusted for relevant biological and lifestyle covariates, we report no association between increased arsenic methylation and metabolic syndrome in a population in which arsenic is regulated at 10 ppb in drinking water. However, we cannot rule out the possibility of a positive association between arsenic methylation and metabolic syndrome in a subsample of women with normal body mass index (BMI). To our knowledge this is the first investigation of arsenic methylation capacity with respect to metabolic syndrome in a low exposure population. We also report that methylation patterns in our sample are similar to those found in highly exposed populations. Additionally, we report that gender and BMI significantly modify the effect of arsenic methylation on metabolic syndrome. Future studies should evaluate the effectiveness of arsenic policy enforcement on subclinical biomarkers of cardiovascular disease.


Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro.
Previously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral cavernous nerve injury (BCNI) and that galanin and its receptors were expressed in nitrergic erectile innervation. Galanin has been observed to exert neuroregenerative effects in dorsal root ganglion neurons, but evidence for these effects in the major pelvic ganglion (MPG) after BCNI is lacking. To evaluate the neurotropic effects of galanin receptor agonists and antagonists in vitro in nitrergic neurons and MPG and in vivo in rats after BCNI. Male Sprague-Dawley rats underwent BCNI and sham surgery. Organ culture and single-cell neuron culture of the MPG were performed. Osmotic pump treatment with the galanin agonist in vivo and measurement of erectile response to electrostimulation after BCNI, immunohistochemical localization of galanin and receptors in the human neurovascular bundle, and myographic analysis of rat corpus cavernosum smooth muscle relaxation to galanin receptor agonists were investigated. Neurite outgrowth in vitro and erectile response to electrostimulation after BCNI in vivo, immunohistochemical localization of galanin and receptors, and penile muscle relaxation in vitro. Galanin showed neurotrophic action in vitro and inhibition of endogenous galanin significantly impaired neurite outgrowth in nitrergic but not in sympathetic MPG neurons. In vivo administration of a selective galanin receptor-2 agonist, M1145, resulted in partial recovery of erectile function (EF) after BCNI. Galanin did not act as a direct vasodilator on corpus cavernosum muscle strips. Endogenous neurotrophins such as galanin could be used as a strategy to improve EF for patients after BCNI from radical prostatectomy. We evaluated the effect of galanin on nerve regeneration and EF recovery in vivo and in vitro. Limitations include the lack of washout period for the in vivo experiment and absence of differences in the expression of neuronal markers between treatment groups. We identified galanin as a potential endogenous mechanism for nerve regeneration after BCNI, which could play a physiologic role in EF recovery after radical prostatectomy. In vivo treatment with exogenous galanin was beneficial in enhancing EF recovery after BCNI, but further research is necessary to understand the underlying mechanisms. Weyne E, Hannan JL, Gevaert T, et al. Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro. J Sex Med 2018;15:480-491.


Assessment of the disease severity in patients hospitalized for COVID-19 based on the National Early Warning Score (NEWS) using statistical and machine learning methods: An electronic health records database analysis.
The coronavirus disease 2019 (COVID-19) was a cause of concern in the healthcare system and increased the need for disease severity indicators. However, they still vary in use to evaluate in-hospital outcomes and severity. The National Early Warning Score (NEWS) is routinely used to evaluate patient health status at the hospital. Further research is needed to ensure if NEWS can be a good instrument for an overall health status assessment with or without additional information like laboratory tests, intensive care needs, and history of chronic diseases. To evaluate if NEWS can be an indicator to measure COVID-19 patient status in-hospital. We used the fully anonymized Electronic Health Records (EHR) characterizing patients admitted to the hospital with COVID-19. Data was obtained from Vilnius University Hospital Santaros Klinikos EHR system (SANTA-HIS) from 01-03-2020 to 31-12-2022. The study sample included 3875 patients. We created several statistical and machine learning models for discrimination between in-hospital death/discharge for evaluation NEWS as a disease severity measure for COVID-19 patients. In these models, two variable sets were considered: median NEWS and its combination with clinical parameters and medians of laboratory test results. Assessment of models' performance was based on the scoring metrics: accuracy, sensitivity, specificity, area under the ROC curve (AUC), and F1-score. Our analysis revealed that NEWS predictive ability for describing patient health status during the stay in the hospital can be increased by adding the patient's age at hospitalization, gender, clinical and laboratory variables (0.853 sensitivity, 0.992 specificity and F1-score - 0.859) in comparison with single NEWS (0.603, 0.995, 0.719, respectively). A comparison of different models showed that stepwise logistic regression was the best method for in-hospital mortality classification. Our findings suggest employing models like ours for advisory routine usage. Our model demonstrated incremental value for COVID-19 patient's status evaluation.


Prevalence and correlates of dental caries among 2-5 years children with special reference to breastfeeding in Kamrup District, Assam.
Dental caries among children is one of the most common health-related issues worldwide. To find out the prevalence of dental caries among 2-5 years old children in Kamrup district of Assam with reference to breastfeeding and associated variables. In this community-based cross-sectional study, 1439 children were examined from 15 wards of Kamrup Metro and four randomly chosen blocks of Kamrup Rural. Children were examined to assess the mean decayed/filled primary teeth (dmft) index, and a self-administered validated questionnaire was given to the mothers to collect data on the practice of breastfeeding initiation, its duration, and dental hygiene habits. Dental caries prevalence was found to be higher in urban areas (54.6%) than rural areas (45.4%). The frequency of using toothpaste was highest among the tooth-cleaning materials. A significant difference in caries prevalence was observed among the children, those who brushed twice a day, and those who did not brush (P = 0.039). The difference was significant in the mean dmft of children from the upper socioeconomic class (P = 0.023) compared with the other classes. A significant difference was also observed between breastfeeding duration (P = 0.010), exclusive and nonexclusive breastfeeding, time of initiation of breastfeeding within 12 h (P < 0.001), and alternative feeding with caries prevalence (P < 0.001). Dental caries were higher in urban localities and upper socioeconomic classes. Breastfeeding initiation and duration may play an important role in the causation of dental caries. No significant association was found between colostrum, prelacteal feeding, and caries prevalence.


[Hematology in the time of COVID-19].
The COVID-19 pandemic impacts the hematology practice. Intensive chemotherapies for high-grade lymphomas and acute leukemias, multiple myeloma treatments and most hematopoietic stem cell transplantations should be performed as usual. Low-grade lymphomas should only be treated when strictly indicated, maintenance can be postponed. Other myeloid neoplasia and their therapies cause imunosupression; dose adjustment is recommended but no brisk stopping. Sickle cell anemia patients are highly succeptible to severe COVID-19 course. Thrombocytopenia and procoagulant state are associated with severe courses of COVID-19, requiring an individualized therapy. No data indicate a risk of SARS-CoV-2 transmission through blood product transfusion.


Karakousis's abdominoinguinal approach for the treatment of a primary retroperitoneal parasitic leiomyoma with inguinal extension. A case report.
Primary retroperitoneal parasitic leiomyoma (PRPL) with inguinal extension is a diagnostic-therapeutic challenge due to its uncertain etiopathogenesis and because it has been considered unresectable according to customary surgical techniques in some instances. The abdominoinguinal incision described by Karakousis in the 1980s allows a safe and radical approach for lower quadrants abdominopelvic tumors. We present the case of a rare PRPL satisfactorily treated through Karakousis's approach. A 35-year-old woman was referred from the Gynecology Service to our Unit. She suffered from a pelvic tumor with left inguinal extension. Initially, it was diagnosed as a retroperitoneal sarcomatous tumor as any digestive and/or gynecological origins of the pelvic tumor were excluded. A radical oncologic excision with permanent neuro-vascular control was undertaken using a left Karakousis's abdominoinguinal approach. The final anatomopathological report was PRPL. The patient was discharged after 8 days. She is disease-free 18 months later. PRPL variant could be related to remnant embryogenic cells of the ducts of Wolf and Müller. Karakousis's approach allowed an en-bloc ilioinguinal removal of the tumor in continuity, with permanent control of the aorto-ileo-femoral axis, the sparing of the neuro-vascular package, and ensured a total abdominal wall restoration. PRPL is a rare extrauterine entity probably derived from remnant embryogenic cells. The absence of clinical guidelines recommend an individualized treatment of these patients. Karakousis's abdominoinguinal approach should be present in any surgeon's armamentarium as the resectability-rate of tumors of the lower quadrant of the abdomen increases up to 95%.


Integrated unsupervised-supervised modeling and prediction of protein-peptide affinities at structural level.
Cell signal networks are orchestrated directly or indirectly by various peptide-mediated protein-protein interactions, which are normally weak and transient and thus ideal for biological regulation and medicinal intervention. Here, we develop a general-purpose method for modeling and predicting the binding affinities of protein-peptide interactions (PpIs) at the structural level. The method is a hybrid strategy that employs an unsupervised approach to derive a layered PpI atom-residue interaction (ulPpI[a-r]) potential between different protein atom types and peptide residue types from thousands of solved PpI complex structures and then statistically correlates the potential descriptors with experimental affinities (KD values) over hundreds of known PpI samples in a supervised manner to create an integrated unsupervised-supervised PpI affinity (usPpIA) predictor. Although both the ulPpI[a-r] potential and usPpIA predictor can be used to calculate PpI affinities from their complex structures, the latter seems to perform much better than the former, suggesting that the unsupervised potential can be improved substantially with a further correction by supervised statistical learning. We examine the robustness and fault-tolerance of usPpIA predictor when applied to treat the coarse-grained PpI complex structures modeled computationally by sophisticated peptide docking and dynamics simulation. It is revealed that, despite developed solely based on solved structures, the integrated unsupervised-supervised method is also applicable for locally docked structures to reach a quantitative prediction but can only give a qualitative prediction on globally docked structures. The dynamics refinement seems not to change (or improve) the predictive results essentially, although it is computationally expensive and time-consuming relative to peptide docking. We also perform extrapolation of usPpIA predictor to the indirect affinity quantities of HLA-A*0201 binding epitope peptides and NHERF PDZ binding scaffold peptides, consequently resulting in a good and moderate correlation of the predicted KD with experimental IC50 and BLU on the two peptide sets, with Pearson's correlation coefficients Rp = 0.635 and 0.406, respectively.


Preparation of dexamethasone ophthalmic implants: a comparative study of in vitro release profiles.
Diseases affecting the posterior segment of the eye are the most common cause of visual disorders in industrialized countries. This scenario has encouraged the development of new treatment modalities for these diseases, such as drug loaded implants with prolonged drug release. The aim of the present work was to create a polymeric based biodegradable ophthalmic implant for the delivery of dexamethasone. For this purpose, we prepared and compared the in vitro release profiles of dexamethasone ophthalmic implants produced by two methods: melting casting and solvent casting. The type of the biodegradable polymer used - poly (ɛ-caprolactone) (PCL) and poly(lactic acid) (PLA); the drug loading (10% and 25%, w/w), the molecular weight of PCL (37 kDa and 14 kDa) and the form of the drug (dexamethasone and dexamethasone disodium phosphate) were also investigated. The results show that the preparation method has little influence on the obtained release profiles, being the type of polymer the most significant factor affecting the release profiles; nonetheless, a better distribution of dexamethasone was obtained for the devices prepared by melting casting.


Transplantation in diabetic kidney failure patients: modalities, outcomes, and clinical management.
Diabetes mellitus (DM) is a common and devastating disease, affecting up to 19.3 million Americans. It is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States. Diabetic patients with ESRD have a high incidence of cardiovascular disease and death. For those kidney transplant patients with no history of DM prior to transplantation, the development of new onset diabetes after transplantation (NODAT) also poses a serious threat to both graft and patient survival. Kidney transplantation is the best renal replacement option for diabetic ESRD and has the potential to halt the progression of cardiovascular diseases. Early referral for transplant evaluation is essential for pre-emptive or early kidney transplantation in this cohort of patients. In type 1 DM patients with ESRD, simultaneous pancreas and kidney transplantation (SPK) should be encouraged; and in patients facing prolonged waiting time for SPK transplantation but with an available living donor, living donor kidney transplantation followed by pancreas after kidney transplantation (PAK) is a suitable alternative. Islet transplantation in type 1 diabetics is deemed experimental by Medicare, and easy access to this modality remains restricted to qualified patients enrolled in clinical trials or with private insurance. The optimal management of kidney transplant patients with pre-existent DM or NODAT involves a multi-pronged approach consisting of pharmacological and nonpharmacological intervention to address all potential cardiovascular risk factors such as glycemic and lipid control, blood pressure control, weight loss, and smoking cessation. Finally, re-transplantation should be recommended in suitable kidney transplant patients when the kidney allograft demonstrates continuous and progressive decline in function.


Hysterectomies. Where are the indications?
This article reviews the major reasons for hysterectomies and critiques some of the alternative practices, such as medical therapy to shrink fibroids, and new surgical techniques, such as laparoscopic-assisted hysterectomies. Perhaps in response to the increased attention and the new procedures and drugs that allow more conservative management, the rate of hysterectomies has actually decreased.


Aura in trigeminal autonomic cephalalgia is probably mediated by comorbid migraine with aura.
The presence of aura is rare in cluster headache, and even rarer in other trigeminal autonomic cephalalgias. We hypothesized that the presence of aura in patients with trigeminal autonomic cephalalgias is frequently an epiphenomenon and mediated by comorbid migraine with aura. The study retrospectively reviewed 480 patients with trigeminal autonomic cephalalgia in a tertiary medical center for 10 years. Phenotypes and temporal correlation of aura with headache were analyzed. Trigeminal autonomic cephalalgia patients with aura were further followed up in a structured telephone interview. Seventeen patients with aura (3.5%) were identified from 480 patients with trigeminal autonomic cephalalgia, including nine with cluster headache, one with paroxysmal hemicrania, three with hemicrania continua, and four with probable trigeminal autonomic cephalalgia. Compared to trigeminal autonomic cephalalgia patients without aura, trigeminal autonomic cephalalgia patients with aura were more likely to have a concomitant diagnosis of migraine with aura (odds ratio [OR] = 109.0, 95% CI 30.9-383.0, p < 0.001); whereas the risk of migraine without aura remains similar between both groups (OR = 1.10, 95% CI = 0.14-8.59, p = 0.931). Aura was more frequently accompanied with migraine-like attacks, but not trigeminal autonomic cephalalgia attacks. In most patients with trigeminal autonomic cephalalgia, the presence of aura is mediated by the comorbidity of migraine with aura. Aura directly related to trigeminal autonomic cephalalgia attack may exist but remains rare. Our results suggest that aura may not be involved in the pathophysiology of trigeminal autonomic cephalalgia.


Burnout in trauma and orthopaedics: a cross-sectional study of surgeons from across the United Kingdom.
Improving psychological wellbeing in healthcare professionals has demonstrable links with improvements in system-performance and patient outcomes. The aims of this study were to determine the prevalence of burnout among orthopaedic surgeons within the United Kingdom (UK) and to identify any influencing factors. This prospective, cross-sectional nationwide study used the Oldenburg Burnout Inventory to assess burnout among orthopaedic registrars, middle grades and consultants from across the UK. In total, 369 participants completed an anonymised online survey. Reasons for burnout were assessed using a list of 20 stressors followed by a white-space box for elaboration. Respondents included 204 (55.3%) consultants, 100 (27.1%) registrars and 65 (17.6%) who were an associate specialist, trust grade or fellow. Some 252 (68.3%) participants experienced moderate-level burnout and 81 (22.0%) high-level burnout. There was no significant association between burnout and grade (p = 0.283), gender (p = 0.433), marital status (p = 0.932), years since graduation (p = 0.397), overseas training (p = 0.642), hours worked (p = 0.601), region (p = 0.699) or hospital type (p = 0.813). A high level of disengagement and exhaustion were identified, with the latter being a greater contributory factor. The most common reasons for burnout were insufficient staff numbers, an overload of administrative work and limited time to see patients. There was a moderate to high level of burnout among orthopaedic surgeons within the UK. Clinical and management teams should focus on improving staff numbers, reducing administrative work and increasing clinic consultation times to limit any further disengagement and exhaustion from surgeons. Reducing burnout may help to improve mental wellbeing, work satisfaction and workforce productivity.


Iron, Cobalt, and Nickel Phthalocyanine Tri-Doped Electrospun Carbon Nanofibre-Based Catalyst for Rechargeable Zinc-Air Battery Air Electrode.
The goal of achieving the large-scale production of zero-emission vehicles by 2035 will create high expectations for electric vehicle (EV) development and availability. Currently, a major problem is the lack of suitable batteries and battery materials in large quantities. The rechargeable zinc-air battery (RZAB) is a promising energy-storage technology for EVs due to the environmental friendliness and low production cost. Herein, iron, cobalt, and nickel phthalocyanine tri-doped electrospun carbon nanofibre-based (FeCoNi-CNF) catalyst material is presented as an affordable and promising alternative to Pt-group metal (PGM)-based catalyst. The FeCoNi-CNF-coated glassy carbon electrode showed an oxygen reduction reaction/oxygen evolution reaction reversibility of 0.89 V in 0.1 M KOH solution. In RZAB, the maximum discharge power density (Pmax) of 120 mW cm-2 was obtained with FeCoNi-CNF, which is 86% of the Pmax measured with the PGM-based catalyst. Furthermore, during the RZAB charge-discharge cycling, the FeCoNi-CNF air electrode was found to be superior to the commercial PGM electrocatalyst in terms of operational durability and at least two times higher total life-time.


Dental prosthetic treatment needs of inpatients with schizophrenia in Taiwan: a cross-sectional study.
The need to obtain information on the dental prosthetic treatment needs (DPTNs) of inpatients with schizophrenia is unrecognized. This study aims to assess the DPTNs of this population and investigate the association between these needs and related factors. The results of an oral health survey involving 1,103 schizophrenic adult inpatients in a long-term care institution in Taiwan were used. Chi-square tests and multiple logistic analyses were used to measure the independent effects of the characteristics of each subject on their DPTNs. Of the subjects, 805 (73.0%) were men and 298 (27.0%) were women. The mean age was 50.8 years. A total of 414 (37.5%) required fixed prosthesis, whereas 700 (63.5%) needed removable prosthesis. Multivariate analyses show that fixed prosthesis is associated with age only after adjusting for other potential independent variables. Older subjects who had a lower educational attainment or a longer length of stay required removable prosthesis. The findings of this study show that the DPTNs of schizophrenic inpatients are not being met. Therefore, a special approach to the dental prosthetic treatment of these patients should be developed.


Microbiota and Derived Parameters in Fecal Samples of Infants with Non-IgE Cow's Milk Protein Allergy under a Restricted Diet.
Cow's milk protein allergy (CMPA) is the most common food allergy in infancy. Non-IgE mediated (NIM) forms are little studied and the responsible mechanisms of tolerance acquisition remain obscure. Our aim was to study the intestinal microbiota and related parameters in the fecal samples of infants with NIM-CMPA, to establish potential links between type of formula substitutes, microbiota, and desensitization. Seventeen infants between one and two years old, diagnosed with NIM-CMPA, were recruited. They were all on an exclusion diet for six months, consuming different therapeutic protein hydrolysates. After this period, stool samples were obtained and tolerance development was evaluated by oral challenges. A control group of 10 age-matched healthy infants on an unrestricted diet were included in the study. Microbiota composition, short-chain fatty acids, calprotectin, and transforming growth factor (TGF)-β₁ levels were determined in fecal samples from both groups. Infants with NIM-CMPA that consumed vegetable protein-based formulas presented microbiota colonization patterns different from those fed with an extensively hydrolyzed formula. Differences in microbiota composition and fecal parameters between NIM-CMPA and healthy infants were observed. Non-allergic infants showed a significantly higher proportion of Bacteroides compared to infants with NIM-CMPA. The type of protein hydrolysate was found to determine gut microbiota colonization and influence food allergy resolution in NIM-CMPA cases.


Do noninherited maternal antigens (NIMA) enhance renal graft survival?
To test the hypothesis that noninherited maternal antigens (NIMA) can modulate the alloreactivity of infant cells and provide protection for renal transplant recipients, a study of renal transplantations performed between 1980 and 1991 was undertaken. The survival rate of grafts with a mismatched antigen identical to the NIMA was compared to that of grafts in which the mismatched antigen was not identical to the NIMA. In the case of HLA-A mismatches, graft survival rates were significantly better for NIMA-mismatched transplants: 94% and 83% at 1 and 3 years, respectively, for single NIMA HLA-A mismatched transplants, and 83% and 67% when both HLA-A antigens were mismatched, compared to 76% and 68% (one non NIMA HLA-A mismatch) and 67% and 45% (two non-NIMA HLA-A mismatches). Our results suggest that some class I NIMA-mismatched antigens are not harmful to renal transplant recipients.


Fibro-osteochondroma of the uterus.
A case of a uterine fibro-osteochondroma in a 61-year-old woman with postmenopausal bleeding was presented. Ultrasound revealed a calcified lesion in the posterior wall of the uterus and a hysterectomy was performed. Histopathologic examination showed a well-circumscribed triphasic tumor composed of peripheral lobules of mature hyaline cartilage and foci of trabecular bone with a core of loosely arranged fibroblast-like, spindle cells. This is the second reported case of fibro-osteochondroma, which has been described only in the uterus. Diagnosis requires thorough histopathologic examination to exclude metaplasia within a leiomyoma or uterine sarcoma. It is histologically benign and complete excision should be curative.


Deficiency of Both Farnesoid X Receptor and Takeda G Protein-Coupled Receptor 5 Exacerbated Liver Fibrosis in Mice.
Activation of the nuclear bile acid receptor farnesoid X receptor (FXR) protects against hepatic inflammation and injury, while Takeda G protein-coupled receptor 5 (TGR5) promotes adipose tissue browning and energy metabolism. Here, we examined the physiological and metabolic effects of the deficiency of these two bile acid receptors on hepatic metabolism and injury in mice. Fxr/Tgr5 double knockout mice (DKO) were generated for metabolic phenotyping. Male DKO mice fed a chow diet had reduced liver lipid levels but increased serum cholesterol levels. Liver cholesterol 7α-hydroxylase (Cyp7a1) activity and sterol 12α-hydroxylase mRNA levels were induced, while ileum FXR target genes were suppressed in DKO mice compared to wild-type (WT) mice. Bile acid pool size was increased in DKO mice, with increased taurocholic acid and decreased tauromuricholic acids. RNA sequencing analysis of the liver transcriptome revealed that bile acid synthesis and fibrosis gene expression levels are increased in chow-fed DKO mice compared to WT mice and that the top regulated pathways are involved in steroid/cholesterol biosynthesis, liver cirrhosis, and connective tissue disease. Cholestyramine treatment further induced Cyp7a1 mRNA and protein in DKO mice and increased bile acid pool size, while cholic acid also induced Cyp7a1 in DKO mice, suggesting impaired bile acid feedback regulation. A Western diet containing 0.2% cholesterol increased oxidative stress and markers of liver fibrosis but not hepatic steatosis in DKO mice. Conclusion: FXR and TGR5 play critical roles in protecting the liver from inflammation and fibrosis, and deficiency of both of these bile acid receptors in mice increased cholic acid synthesis and the bile acid pool, liver fibrosis, and inflammation; FXR and TGR5 DKO mice may be a model for liver fibrosis.