The liver in Hodgkin's disease--I. Clinico-pathological relations.
A retrospective analysis of staging results from 308 patients with Hodgkin's disease (HD) was performed in order to relate clinico-pathological findings with respect to the liver to other staging results and to prognosis. Thirty-four patients had clinically enlarged liver, 80 had increased serum-enzyme levels indicating possible liver damage, but only 10 patients had biopsy-proven histologic evidence of HD in the liver (7 primary biopsies, 3 re-biopsies). Among the prognostic correlations not only advanced stage and liver infiltrates were connected to poor prognosis, but also--even in early stages--elevated serum enzyme values (S-GOT and alkaline phosphate).


Barriers to access and utilisation of sexual and reproductive health services among adolescents in Ethiopia: a sequential mixed-methods study.
To investigate and explore the barriers of access and utilisation of sexual and reproductive health (SRH) services among adolescents. An explanatory sequential mixed-methods design was implemented with two phases. The questionnaire was created and used by five trained research assistants for the quantitative component of the study (phase I). In phase II, the qualitative component of the study included focus group discussions (FGDs) with adolescents. This study was conducted in rural areas of five secondary schools in Arsi zone, Ethiopia. In both phases, 15-19 years adolescents participated in the study. For the quantitative phase, a total of 800 randomly selected adolescents responded to the questionnaire, while 24 adolescents participated during FGDs until data saturation was reached. For outcome variables, the respondents were asked if they used any SRH services in the past 12 months. It was recorded as 0=no and 1=yes. Overall, SRH service utilisation was 208 (26.1%) among adolescents. Being aged 17-19 years (adjusted OR, AOR 3.44, 95% CI 2.15 to 5.51). Grades 11 and 12 (AOR 2.70, 95% CI 1.22 to 2.32). Lack of income (AOR 0.0.43, 95% CI 0.31 to 0.61). Ever had sexual contact (AOR 3.04 CI 95% CI 2.15 to 4.29) and being knowledgeable on SRH service (AOR 1.47, 95% CI 1.05 to 2.05) were factors associated with outcome variable. The barriers hindering access and use of SRH services were found at the facility level, provider level, community level and personal level. The research found a low level of SRH services access and utilisation among adolescents due to several factors. Interventions to design-specific policies and educational programmes are needed to promote healthy practices.


Ross procedure and left ventricular mass regression.
Return of left ventricular mass to normal is considered to be a favorable result of aortic valve replacement. The Ross procedure provides near normal hemodynamics and thus allows studies of left ventricular (LV) reverse remodeling. LV mass regression may be influenced by surgical technique (subcoronary [SC] versus root replacement [RR]). Data from the German Ross Registry were analyzed. A total of 646 patients (mean age: 43.6+/-12.7 years, range: 16 to 71 years; SC technique n=295, RR technique n=351) underwent a Ross procedure in 7 participating centers from 1990 to 2004. The patients underwent preoperative and postoperative echocardiographic evaluations. Mean follow-up time was 3.5+/-2.5 years (range 0.12 to 13.7 years). Follow-up completeness was 97%. The LV mass index (LVMI) decreased significantly during follow-up in both groups (SC: 209+/-53 preoperatively to 154+/-48 at 1-year follow-up, [P<0.01 versus preoperative values] to 149+/-51 g/m2 at 2-year follow-up, [P=NS 1-year versus 2-year follow-up] versus RR: from 195+/-56 preoperatively to 144+/-51 at 1-year follow-up [P<0.01 versus preoperative values] to 140+/-49 g/m2 [P=NS 1-year versus 2-year follow-up]). LVMI regression remained stagnant 1 year after the Ross procedure in most patients in both groups. On the basis of multivariate analysis, predictors for incomplete LVMI regression after the autograft procedure were high preoperative LVMI, smoking, and uncontrolled diastolic hypertension. At mid-term echocardiographic follow-up, patients of both groups had favorable autograft hemodynamics. Risk factors for incomplete postoperative LVMI regression in our study were smoking and persistent diastolic hypertension. This emphasizes the importance of cessation of smoking and treatment of arterial hypertension, even in younger patients, after corrected aortic valve disease.


Association between three-year mortality after transcatheter aortic valve implantation and paravalvular regurgitation graded by videodensitometry in comparison with visual grading.
Estimation of regurgitant fraction by videodensitometry (VD-AR) of aortic root angiograms is a new tool for objective grading of paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI). Stratification with boundaries at 6% and 17% has been proposed to reflect "none/trace", "mild" and "moderate or higher" PVR. We sought to investigate the association of strata of VD-AR with 3-year mortality and to compare VD-AR with visual grading of angiograms. We interrogated our database for patients undergoing transfemoral TAVI from 2008 to 2018. Vital status of the patients was obtained from population registers. To test differences in survival and estimate adjusted hazard ratios (HRs) we fitted Cox models. Our retrospective study included 699 patients with evaluable angiograms at completion of the TAVI procedure. Cumulative 3-year mortality was 35.0% in 261 (37.3%) patients with VD-AR < 6%, 33.9% in 325 (46.5%) patients with VD-AR between 6 and 17% (HR [95% confidence interval] 1.06 [0.80-1.42]; P = 0.684) and 47.2% in 113 (16.2%) patients with VD-AR > 17% (HR 1.57 [1.11-2.22]; P = 0.011). Visually, PVR was graded as "none/trace" in 470 (67.2%) patients, as "mild" in 219 (31.3%) and as "moderate" in 10 (1.4%). Both mild PVR and moderate PVR on visual grading were significantly associated with mortality (HRs 1.31 [1.12-1.54]; P = 0.001 and 1.92 [1.13-3.24]; P = 0.015; respectively). VD-AR > 17%, but not VD-AR 6-17%, was independently associated with mortality. Compared with subjective visual evaluation, VD-AR resulted in a smaller proportion of patients with PVR classified as prognostically relevant.


Test-retest reliability in an fMRI study of naming in dementia.
fMRI has been used as an outcome measure in dementia treatment studies, with many previous studies comparing only single pre- and post-treatment fMRI scans to determine treatment-induced neural changes, while utilizing single subject experimental designs. The purpose of the current study was to evaluate fMRI test-retest reliability in dementia patients and typical older adults using noun and verb confrontation naming to evaluate the validity of using a single pre/post-treatment scan comparison. Seven individuals with dementia and 9 control participants were tested three times over two months using the same fMRI procedures. Differences in individual and group level activation patterns were observed that varied across time. Additionally, the extent of variability fluctuated across individuals, groups, and the grammatical category of target words. Our findings suggested that one time fMRI scanning may inadequately represent an individual's typical brain activation pattern, particularly an individual with dementia. Thus, multiple imaging baselines are recommended.


Cyclodextrin polysulphates repress IL-1 and promote the accumulation of chondrocyte extracellular matrix.
To evaluate the influence of cyclodextrin polysulphate (CDPS) on the extracellular matrix (ECM) metabolism of human articular cartilage chondrocytes. Isolated chondrocytes from femoral condyle cartilage of human knee joints were cultured in gelled alginate to maintain their differentiated phenotype. During 1 week of culture, the cells were exposed to different concentrations of CDPS. Synthesis of aggrecans was investigated in these cultures after using Na(2)(35)SO(4) as a radioactive precursor during the last 24h of culture. The artificial matrix was then solubilised with Na-citrate and newly synthesised aggrecan aggregates, accumulated during culture, were liberated and assayed. The isolated chondrocytes were labelled with antibodies against aggrecan and type II collagen to analyse the ECM molecules in the cell-associated matrix (CAM). Plasma membrane levels of receptors for insulin-like growth factor-1 (IGF-1RI) and for interleukin-1 (IL-1RI and IL-1RII), as well as levels of IGF-1, IL-1alpha and -beta were determined after the cells had been permeabilized and stained with the appropriate antibodies. The release of IL-6 in the culture media was used as a variable reflecting auto/paracrine IL-1 activity of the cells in different experimental conditions. CDPS significantly increased total (35)S-incorporation rates in ECM aggrecan. When compared with controls, CDPS-treated chondrocytes expressed significantly higher CAM aggrecan and type II collagen levels. As plasma membrane-bound IGFR1 and intracellular IGF-1 levels remained unchanged, this increase in accumulated CAM compounds may have resulted from suppressed catabolic activities by the chondrocytes in culture. CDPS-treated cells expressed significantly lower amounts of intracellular IL-1alpha and -beta levels. Plasma membrane-bound IL-1RI and decoy IL-1RII remained unchanged. beta-cyclodextrin-treated chondrocytes released significantly less IL-6 in the supernatant culture media. CDPS is a novel polysulfated polysaccharide showing cartilage structure modifying effects in vitro as it improves the synthesis of aggrecan and the accumulation of CAM macromolecules. This effect probably resulted in part from the downregulation of IL-1.


Trait/Financial Information of Potential Male Mate Eliminates Mate-Choice Copying by Women: Trade-Off Between Social Information and Personal Information in Mate Selection.
Mate-choice copying occurs when people rely on the mate choices of others (social information) to inform their own mate decisions. The present study investigated women's strategic trade-off between such social learning and using the personal information of a potential mate. We conducted two experiments to investigate how mate-choice copying was affected by the personal information (e.g., trait/financial information, negative/positive valence of this information, and attractiveness) of a potential male mate in short-/long-term mate selection. The results demonstrated that when women had no trait/financial information other than photos of potential mates, they showed mate-choice copying, but when women obtained personality trait or financial situation information (no matter negative or positive) of a potential mate, their mate-choice copying disappeared; this effect was only observed for low-attractiveness and long-term potential partners. These results demonstrated human social learning strategies in mate selection through a trade-off between social information and personal information.


NEWSTART: An 8-Week Faith-Based Health Promotion Program to Reduce Chronic Disease Risk Factors in the US.
This single-group experimental study examined the effectiveness of NEWSTART, an 8-week health promotion program among adults in an Adventist Faith Community. Participants had a significant reduction in diastolic blood pressure [Formula: see text] with a moderate effect size (Cohen d = 0.68), reduction of daily sugar-sweetened beverage intake [Formula: see text] with a large effect size (Cohen d = 0.96), and an improvement in weekly moderate intensity exercise [Formula: see text] with a large effect size (Cohen d = .83). Participants met the fruit and vegetable intake recommendations and applying program principles to reduce chronic disease risk factors.


A Predicted Model for Refractory/Recurrent Cytomegalovirus Infection in Acute Leukemia Patients After Haploidentical Hematopoietic Stem Cell Transplantation.
We aimed to establish a model that can predict refractory/recurrent cytomegalovirus (CMV) infection after haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT). Consecutive acute leukemia patients receiving HID HSCT were enrolled (n = 289). We randomly selected 60% of the entire population (n = 170) as the training cohort, and the remaining 40% comprised the validation cohort (n = 119). Patients were treated according to the protocol registered at https://clinicaltrials.gov (NCT03756675). The model was as follows: Y = 0.0322 × (age) - 0.0696 × (gender) + 0.5492 × (underlying disease) + 0.0963 × (the cumulative dose of prednisone during pre-engraftment phase) - 0.0771 × (CD34+ cell counts in graft) - 1.2926. The threshold of probability was 0.5243, which helped to separate patients into high- and low-risk groups. In the low- and high-risk groups, the 100-day cumulative incidence of refractory/recurrent CMV was 42.0% [95% confidence interval (CI), 34.7%-49.4%] vs. 63.7% (95% CI, 54.8%-72.6%) (P < 0.001) for total patients and was 50.5% (95% confidence interval (CI), 40.9%-60.1%) vs. 71.0% (95% CI, 59.5%-82.4%) (P = 0.024) for those with acute graft-versus-host disease. It could also predict posttransplant mortality and survival. We established a comprehensive model that could predict the refractory/recurrent CMV infection after HID HSCT. https://clinicaltrials.gov, identifier NCT03756675.


Feasibility evaluation of a dual-mode ankle exoskeleton to assist and restore community ambulation in older adults.
Age-related deficits in plantar flexor muscle function during the push-off phase of walking likely contribute to the decline in mobility that affects many older adults. Isolated strengthening of the plantar flexor muscles has failed to improve push-off power or walking economy in this population. New mobility aids and/or functional training interventions may help slow or prevent ambulatory decline in the elderly. The overarching objective of this study was to explore the feasibility of using an untethered, dual-mode ankle exoskeleton for treating walking disability in the elderly; testing the device in assistance mode as a mobility aid to reduce energy consumption, and as a resistive gait training tool to facilitate functional recruitment of the plantar flexor muscles. We recruited 6 older adults between the ages of 68 to 83 years to evaluate the feasibility of the dual-mode exoskeleton across two visits. On the first visit, we quantified acute metabolic and neuromuscular adaption to ankle exoskeleton assistance during walking in older adults, and subsequently determined if higher baseline energy cost was related to an individual's potential to benefit from untethered assistance. On the second visit, we validated the potential for push-off phase ankle resistance combined with plantar pressure biofeedback to facilitate functional utilization of the ankle plantar flexors during walking. We also conducted a twelve-session ankle resistance training protocol with one pilot participant to explore the effects of gait training with wearable ankle resistance on mobility and plantar flexor strength. Participants reached the lowest net metabolic power, soleus variance ratio, and soleus iEMG at 6.6 ± 1.6, 19.8 ± 1.6, and 5.8 ± 4.9 minutes, respectively, during the 30-minute exoskeleton assistance adaptation trial. Four of five participants exhibited a reduction (up to 19%) in metabolic power during walking with assistance relative to baseline, but there was no group-level change. Participants who had greater baseline metabolic power exhibited a greater reduction during walking with assistance. Walking with resistance increased stance-phase soleus iEMG by 18 - 186% and stance-phase average positive ankle power by 9 - 88% compared to baseline. Following ankle resistance gait training, the participant exhibited a 5% increase in self-selected walking speed, a 15% increase in fast walking speed, a 36% increase in 6-min-walk-test distance, and a 31% increase in plantar flexor strength compared to pre-intervention measurements. Our results suggest that dual-mode ankle exoskeletons appear highly applicable to treating plantar flexor dysfunction in the elderly, with assistance holding potential as a mobility aid and resistance holding potential as a functional gait training tool. We used an untethered design to maximize the relevance of this for informing the design of intervention studies that may take place at home and in the community to improve mobility and quality of life in older adults. Future studies with larger sample sizes are recommended to expand on the results of this feasibility investigation.


Influence of pinealectomy on serum estrogen and progesterone levels in blind-anosmic female rats.
Previous studies show that the suppression of gonadal function in blind-anosmic rats is dependent on the pineal gland. The present results demonstrate that in young female rats both the pineal gland and dual sensory deprivation have additional independent antigonadal effects.


Bilateral renal cell carcinoma in a child.
Renal cell carcinoma is a rare renal tumor in the pediatric population with an incidence of 0.1-0.3%. We report on the first case of bilateral renal clear cell carcinoma that was treated by partial nephrectomies. We performed a complete genetic evaluation to exclude a family inheritance and we looked at the deletions associated with the possible histologic subtypes of renal cell carcinoma. The patient had no evidence of recurrence after 80-month follow-up and her renal function remained normal.


Increased interactive format for Morbidity & Mortality conference improves educational value and enhances confidence.
The Mortality and Morbidity (M&M) conference is a staple of surgical training programs. With reduced resident work hours, maximizing limited educational opportunities has become essential. We attempted to determine whether increasing the perceived educational value in M&M conference is associated with enhanced confidence levels in the future. We analyzed which features of M&M case reviews are associated with greater perceived educational value and enhanced confidence to deal with similar future clinical scenarios. Educational process variables were prospectively collected for 47 consecutive cases reviewed over a 16-week period at a single institution's surgical M&M conference. General surgery residents completed self-reporting surveys rating the educational value of cases and impact on confidence in managing similar future clinical situations. Univariate regression analysis and multivariate regression analysis were calculated to study the relationship between various process variables and perceived educational and confidence values surveyed by residents. Tertiary academic medical center. General surgery residents PGY1 to PGY5. Increased perceived educational value was associated with increased confidence (p < 0.001). Perceived educational value was increased with more questioning of the audience, increasing explanations of cases, use of slides, increase in number of questions directed to attendings, use of radiologic images, the more junior the resident surveyed, and when teaching points were made specifically for the medical students in attendance. (p < 0.05) Level of confidence was increased with increased questioning to the audience, increased explanations, increased questioning of the attendings, and more junior the resident surveyed. Increased questioning of presenter did not increase perceived educational value or resident perceived confidence value. These data demonstrate that audience interaction, not directed questioning of the presenter, may improve surgical resident perceived educational value and confidence in managing problems discussed at M&M. These data suggest that M&M moderators can play a central role in maximizing audience interaction and improve the educational value of this important conference.


[Excimer laser-assisted penetrating keratoplasty : On 1 July 2019 excimer laser penetrating keratoplasty celebrates its 30th anniversary. Video article].
Since 1986 Naumann and Lang have developed and optimized the technique of nonmechanical corneal trephination using a 193-nm excimer laser along metal masks for penetrating keratoplasty (PKP). The aim of this paper is to demonstrate the technique of excimer laser-assisted keratoplasty. After beginning with elliptical transplants a major improvement resulted in the introduction of eight "orientation cogs/notches" at the edges of round metal masks for reduction of "horizontal torsion". For noncontact donor trephination from the epithelial side an artificial anterior chamber is used. The surgical technique is demonstrated in detail and in almost full length in a video of the operation, which is available online. Prospective clinical studies have shown that the technique of noncontact excimer laser PKP improves donor and recipient misalignment, reduces "vertical tilt" and "horizontal torsion" of the graft in the recipient bed. This results in significantly less keratometric astigmatism, greater regularity of the topography and better spectacle-corrected visual acuity after removal of the sutures. Besides less perioperative disturbance of the blood-intraocular fluid barrier, excimer laser trephination does not induce enhanced cataract formation and does not impair the graft endothelium. Likewise, the rate of immune reactions is not adversely affected by the excimer laser. Furthermore, trephination of an unstable cornea, such as (nearly) perforated corneal ulcers or after radial keratotomy or LASIK is facilitated. Because of the undisputed clinical advantages, especially in eyes with advanced keratoconus, excimer laser trephination with orientation cogs/notches is currently favored in the routine daily practice in Homburg/Saar.


Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression.
Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by central nervous (CNS) demyelination resulting in axonal injury and neurological deficits. Essentially, MS is driven by an auto-amplifying mechanism of inflammation and cell death. Current therapies mainly focus on disease modification by immunosuppression, while no treatment specifically focuses on controlling cell death injury. Here, we report that ferroptosis, an iron-catalyzed mode of regulated cell death (RCD), contributes to MS disease progression. Active and chronic MS lesions and cerebrospinal fluid (CSF) of MS patients revealed several signs of ferroptosis, reflected by the presence of elevated levels of (labile) iron, peroxidized phospholipids and lipid degradation products. Treatment with our candidate lead ferroptosis inhibitor, UAMC-3203, strongly delays relapse and ameliorates disease progression in a preclinical model of relapsing-remitting MS. In conclusion, the results identify ferroptosis as a detrimental and targetable factor in MS. These findings create novel treatment options for MS patients, along with current immunosuppressive strategies.


Evaluation of a Common Internal Standard Material to Reduce Inter-Laboratory Variation and Ensure the Quality, Safety and Efficacy of Expanded Newborn Screening Results When Using Flow Injection Analysis Tandem Mass Spectrometry with Internal Calibration.
In 2015, the newborn screening (NBS) programmes in England and Wales were expanded to include four additional disorders: Classical Homocystinuria, Isovaleric Acidemia, Glutaric Aciduria Type 1 and Maple Syrup Urine Disease, bringing the total number of analytes quantified to eight: phenylalanine, tyrosine, leucine, methionine, isovalerylcarnitine, glutarylcarnitine, octanoylcarnitine and decanoylcarnitine. Post-implementation, population data monitoring showed that inter-laboratory variation was greater than expected, with 90th centiles varying from 17 to 59%. We evaluated the effect of stable isotope internal standard (IS) used for quantitation on inter-laboratory variation. Four laboratories analysed routine screening samples (n > 101,820) using a common IS. Inter-laboratory variation was determined for the eight analytes and compared with results obtained using an in-house common IS (n > 102,194). A linear mixed-effects model was fitted to the data. Using a common IS mix reduced the inter-laboratory variation significantly (p < 0.05) for five analytes. For three analytes, the lack of significance was explained by use of individual laboratory "calibration factors". For screening programmes where laboratories adhere to single analyte cut-off values (COVs), it is important that inter-laboratory variation is minimised, primarily to prevent false positive results. Whilst the use of a common IS helps achieve this, it is evident that instrument set-up also contributes to inter-laboratory variation.


Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33).
Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. Plasma copeptin, a surrogate for AVP, was measured in baseline samples from patients with type 2 diabetes treated in primary care and included in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort. Samples from 1,328 patients were available; 349 were analysed separately because they used renin-angiotensin-aldosterone system inhibition (RAASi), which influences albumin/creatinine ratio (ACR) and estimated (e)GFR. In the other 979 patients (46% men, age 68 years [58-75], ACR 1.8 mg/mmol [0.9-5.7], eGFR 67 ± 14 ml min(-1) 1.73 m(-2)) baseline copeptin (5.3 pmol/l [3.2-9.5]) was significantly associated with log e [ACR] and eGFR, even after adjustment for sex, age and risk factors for kidney function decline (standardised [std] β 0.13, p < 0.001, std β -0.20, p < 0.001 respectively). Follow-up data were available for 756 patients (6.5 years [4.1-9.6]). Baseline copeptin was associated with increase in ACR (std β 0.09, p = 0.02), but lost significance after adjustment (std β 0.07, p = 0.08). Copeptin was associated with a decrease in eGFR after adjustment (std β -0.09, p = 0.03). The strength of the association of copeptin with change in eGFR was stronger than that of established risk factors for kidney function decline (e.g. BMI, HbA1c). In patients who used RAASi there was a significant association between baseline copeptin and ACR and eGFR, but not with change in ACR and eGFR. In patients with diabetes not using RAASi a higher baseline copeptin concentration is significantly associated with higher baseline ACR and lower eGFR values and with a decline in eGFR during follow-up. This last association is independent of, and stronger than, most traditional risk factors for kidney function decline.


Subcutaneous or visceral adipose tissue expression of the PPARgamma gene is not altered in the fatty (fa/fa) Zucker rat.
We cloned 537 basepairs (bp) of rat partial peroxisome proliferator-activated receptor gamma2 (PPARgamma2) cDNA and examined the effect of fasting or obesity on the expression of two isoforms of rat PPARgamma, gamma1 and gamma2, in either subcutaneous or mesenteric adipose tissue specimens using an RNase A protection assay. In Wistar rats, expression of both isoforms was dramatically reduced after 48 hours of fasting in the two fat tissue specimens. In comparing genetically obese (fa/fa) Zucker rats and lean control rats, no significant difference was observed in expression of the two isoforms in either type of adipose tissue. From these findings, we conclude that the adipose tissue level of rat PPARgamma depends on nutritional deprivation but is not closely associated with either obesity or insulin resistance in obese Zucker rats.


Ichthyosis nigricans: ultrastructural study of the melanin pigmentary disturbances.
Hyperpigmented skin from a 10-year-old white boy with ichthyosis nigricans has been studied. Histological and ultrastructural studies reveal that the hyperpigmentation is related to both epidermal and dermal hypermelanosis. Melanocytes are hyperactive. The different stages of melanosome synthesis and melanisation appear to be normal. Increased dermal pigmentation probably results from a dischargement of the melanin granules into the dermis secondary to melanocyte alterations. Ichthyosis nigricans is a typical example of melanin pigmentary disturbances of the skin, resulting from disturbances in the normal interactions between melanocytes and keratinocytes.


The effects of ischaemia, lysophosphatidylcholine and palmitoylcarnitine on rat heart phospholipase A2 activity.
Phospholipase A2 activity was studied in the isolated rat heart following coronary artery ligation. In both the homogenate and mitochondrial fractions phospholipase A2 activity was significantly depressed at 20 min post ligation in the ischaemic region only. This is at a time of peak lysophospholipid concentration and severity of arrhythmias. No such depression of activity was seen in a crude sarcolemmal fraction, possibly due to washout of inhibitory factors during isolation. Lysophosphatidylcholine and palmitoylcarnitine, two amphiphiles known to accumulate during ischaemia, were both shown to be capable of inhibiting phospholipase A2. It is suggested that lysophospholipid and palmitoylcarnitine accumulation during ischaemia may contribute to the depression of phospholipase A2 activity seen and that the decreased metabolism of lysophospholipids may be of more importance in their accumulation than increased production by phospholipase A2.


Improving Clinic Productivity through a Shared Medical Appointment.
Physicians are increasingly challenged to balance quality health care with fewer resources and limited time. To help achieve this balance, shared medical appointments have been described. We improved clinic-wide access to care by creating a shared medical appointment for minor penile complaints and anomalies. We implemented a shared medical appointment in April 2013. We developed an intake form to efficiently gather patient history, and a standardized presentation to discuss diagnosis, treatment options, risks and benefits. Outcomes assessed included access to care time, the rate at which patients were seen within a target of 28 days, the number of appointments scheduled and patient complaints. To control for provider availability we evaluated the number of vacation days and operating room cases for the sole pediatric urologist. Data were analyzed using the Mann-Whitney U test. The periods of November 2012 to March 2013 and May 2013 to September 2013 were evaluated. There was a statistically significant improvement in median (IQR) access to care, with a decrease from 26.6 days (26.4, 29.4) before to 20 days (17.1, 24.3) after implementation of the shared medical appointment (p=0.0163). The goal access to care standard was met with a median (IQR) of 81.4% (56.7, 82.8) after the shared medical appointment compared to 44.3% (25.0, 46.9) before the shared appointment (p=0.0283). After implementation of the shared medical appointment, more appointments were scheduled per month at 161 (156, 165) vs 128 (120, 130; p=0.1172). We successfully implemented a shared medical appointment and significantly improved our clinic productivity. This program allowed us to improve access to care by almost 1 week and to increase the overall volume of patients seen monthly.


Maximum entropy restoration of blurred and oversaturated Hubble Space Telescope imagery.
A brief introduction to image reconstruction is made and the basic concepts of the maximum entropy method are outlined. A statistical inference algorithm based on this method is presented. The algorithm is tested on simulated data and applied to real data. The latter is from a 1024 × 1024 Hubble Space Telescope image of the binary stellar system R Aquarii, which suffers from both spherical aberration and detector saturation. Under these constraints the maximum entropy method produces an image that agrees closely with observed results. The calculations were performed on the MasPar MP-1 single-instruction/multiple-data computer.


[PEDIATRIC NEPHROLOGY IN THE TIME OF CORONA].
Symptomatic coronavirus 2019 (COVID-19) infection usually presents with upper airway symptoms, but may lead to complications, such as pneumonia and involvement of other organs, or even death. Children often have a mild clinical course or may be asymptomatic, however, a severe complication of multisystem inflammatory syndrome has been described in rare cases. In severe COVID-19 infection, acute kidney injury may manifest even in children without comorbidities. The aim of this review is to present available data on renal involvement in pediatric COVID-19, and disease manifestations in children with underlying chronic kidney disease (CKD) or children receiving immunosuppressive medications due to kidney transplantation or glomerular disease. Although it could be assumed that children with CKD, including immunosuppressed patients, might be a high risk group for infection and severity of COVID-19 disease, this is not supported by current available data.


Totally laparoscopic abdominal aortic aneurysm repair.
On the basis of our previous animal and clinical experience with laparoscopic intra-abdominal vascular reconstructions, and due to the prevalence of abdominal aortic aneurysms (AAA), we have recently broadened our scope to tackle more difficult aortic surgery laparoscopically. We present a case report of our first clinical experience with laparoscopic AAA repair using specialized laparoscopic vascular instrumentation. The patient was an 84-year-old hypertensive male with a 7-cm asymptomatic infrarenal abdominal aortic aneurysm that was discovered incidentally. He presented with postcoronary artery bypass grafting and had moderate chronic obstructive pulmonary disease (COPD). A spiral computed tomograph (CT) angiogram revealed an adequate infrarenal neck and aneurysmal involvement of the proximal iliac arteries. An eight-port transabdominal technique was used with the patient in the supine position. Proximal and distal control was achieved without difficulty. The aneurysm was excluded using endoscopic stapling devices, and an aortobiiliac reconstruction was performed with a 16 x 9-mm bifurcated dacron graft. Estimated blood loss was 1000 ml, and the operative time was approximately 7 hours. The patient was ambulating without assistance on postoperative day 3. Total hospitalization was 7 days (delayed secondarily to postoperative ileus). Minimal quantities of narcotics were required for analgesia. At 6-months follow-up, the patient has palpable peripheral pulses and no complications related to surgery. This case report shows that a completely laparoscopic approach to the abdominal aortic aneurysm is possible using instrumentation specifically designed for laparoscopic vascular surgery. The exact role that laparoscopic techniques will hold in vascular surgery remains to be determined because these procedures are time consuming and technically difficult.


Depression of mesolimbic dopamine transmission and sensitization to morphine during opiate abstinence.
To investigate the role of mesolimbic dopamine (DA) in the mechanism of drug dependence, extracellular DA was monitored by transcerebral dialysis in the caudal nucleus accumbens under basal conditions and after challenge with morphine (5 mg/kg s.c.) in control rats and in rats made dependent on and then deprived of morphine. Withdrawal from morphine resulted in a marked reduction of extracellular DA concentrations from control values at 1, 2, 3, and 5 days of withdrawal. After 7 days of withdrawal, DA output was less, but still significantly, reduced. Challenge with morphine resulted in stimulation of DA output in controls (maximum, 35%), no effect on the first day of withdrawal, and stimulation similar to controls' on days 2 and 7 of withdrawal. On day 5 and, particularly, on day 3 of withdrawal, morphine-induced stimulation of DA output was markedly potentiated (maximum, 100 and 160%, respectively). Changes in the sensitivity of DA transmission to morphine challenge were associated with changes in the behavioral stimulant effects of morphine, with tolerance on day 1 and marked sensitization on days 3 and 5 but also on day 7, when morphine-induced stimulation of transmission was no longer potentiated. The results indicate that repeated morphine administration induces a state of dependence in DA neurons and a short-lasting tolerance followed by an increased sensitivity to its stimulant effects on DA transmission. These changes might play an important role in the development of opiate addiction and in the maintenance of opiate self-administration in dependent subjects.


Prospection of Microfluidics for Local Drug Delivery.
Significant endeavors can be made to develop effective drug delivery systems. Nowadays, many of these novel systems have gained attention as they focus primarily on increasing the bioavailability and bioaccessibility of several drugs to finally minimize the side effects, thus improving the treatment's efficacy. Microfluidics systems are unquestionably a superior technology, which is currently revolutionizing the current chemical and biological studies, providing diminutive chip-scale devices that offer precise dosage, target-precise delivery, and controlled release. Microfluidic systems have emerged as a promising delivery vehicle owing to their potential for defined handling and transporting of small liquid quantities. The latest microfabrication developments have been made for application to several biological systems. Here, we review the fundamentals of microfluidics and their application for local drug delivery.


Molecular diagnostic and surveillance tools for global malaria control.
Malaria is the most devastating parasitic infection in the world, annually causing over 1 million deaths and extensive morbidity. The global burden of malaria has increased over the last several decades, as have rates of imported malaria into non-endemic regions. Rapid and accurate diagnostics are a crucial component of malaria control strategies, and epidemiological surveillance is required to monitor trends in malaria prevalence and antimalarial drug resistance. Conventional malaria diagnostic and surveillance tools can be cumbersome and slow with limitations in both sensitivity and specificity. New molecular techniques have been developed in an attempt to overcome these restrictions. These molecular techniques are discussed with regard to their technical advantages and disadvantages, with an emphasis on the practicality of implementation in malaria-endemic and non-endemic regions.


Dynamic monitoring of active calcification in atherosclerosis by 18F-NaF PET imaging.
The objective was to dynamically monitor the progression of atherosclerotic plaques in ApoE-/- mice with 18F-NaF PET imaging. The ApoE-/- mice were used to develop atherosclerosis models, and the C57BL/6 J mice were used as control. 18F-NaF PET was performed when the mice were 12, 20, and 30 weeks of age. Serum lipids and lipoproteins profiles, inflammatory cytokines, and calcification factors were tested by ELISA. The lipid distribution, morphology, and calcification of plaque were evaluated by Oil Red O, HE, and alizarin red staining. The correlation between imaging and the extent of calcification was analyzed by Pearson correlation analysis. The uptake of 18F-NaF in the aorta was gradually increased with each weekly extension. Compared with the ApoE-/- mice at the age of 12 weeks and 20 weeks, the levels of lipoprotein, inflammatory cytokines, and calcification factors were higher at 30 weeks. In Oil Red O, HE, and alizarin red staining, the extent of the lipid area and calcification increased with time. The correlation analysis showed that the uptake of 18F-NaF in the aorta was related to the extent of calcification. 18F-NaF may dynamically monitor the progression of atherosclerotic plaques and ongoing microcalcification formation.


The effects of tones on PGO waves in slow wave sleep and paradoxical sleep.
Ponto-geniculo-occipital (PGO) waves are macropotential waveforms occurring spontaneously during paradoxical sleep (PS) in the pons, the lateral geniculate body (LGB), and the occipital cortex of the cat. In our earlier work (6, 20) tones elicited waves in the LGB and the occipital cortex during both slow wave sleep (SWS) and PS that resembled PGO waves in form and amplitude. Using a limited and variable number of trials, we observed that these elicited waveforms, which we term elicited PGO waves (PGOE), seemed to decline rapidly in amplitude and probability during SWS but not during PS. The present two experiments served as a more rigorous test of the hypothesis that the rate of habituation of PGOE would be more rapid in SWS. In a first experiment seven cats were studied in up to four sessions in PS and four in SWS; each session consisted of 32 1000-Hz, 90-dB SPL tones lasting 90 ms. We found that (i) the number of PGOE was significantly greater in PS; (ii) the mean amplitude of the waves was greater in PS; (iii) the probability of eliciting a wave tended to decline faster in SWS, but some decline also occurred in PS; and (iv) on the first trial, PGOE were more easily produced in SWS. Results of a second experiment with five cats suggested that the decline in the probability of PGOE in PS was not accounted for by differences in the ease of eliciting them at different times into a PS episode. The role of the dorsal raphe nucleus (DRN) in modulating state-dependent differences in PGOE is discussed.


Radioactive labeling of proteins with an iodinated amidination reagent.
An iodinated phenolic imidoester has been synthesized for the labeling of proteins to high specific activities with radioactive iodine. The main advantage of this two-step labeling method is that it obviates direct contact of the protein with deleterious oxidizing agents, such as chloramine-T, pressent in direct methods of iodinating proteins.


APOBEC3G protects the genome of human cultured cells and mice from radiation-induced damage.
Cytosine deaminases AID/APOBEC proteins act as potent nucleic acid editors, playing important roles in innate and adaptive immunity. However, the mutagenic effects of some of these proteins compromise genomic integrity and may promote tumorigenesis. Here, we demonstrate that human APOBEC3G (A3G), in addition to its role in innate immunity, promotes repair of double-strand breaks (DSBs) in vitro and in vivo. Transgenic mice expressing A3G successfully survived lethal irradiation, whereas wild-type controls quickly succumbed to radiation syndrome. Mass spectrometric analyses identified the differential upregulation of a plethora of proteins involved in DSB repair pathways in A3G-expressing cells early following irradiation to facilitate repair. Importantly, we find that A3G not only accelerates DSB repair but also promotes deamination-dependent error-free rejoining. These findings have two implications: (a) strategies aimed at inhibiting A3G may improve the efficacy of genotoxic therapies used to cure malignant tumours; and (b) enhancing A3G activity may reduce acute radiation syndrome in individuals exposed to ionizing radiation.


Photoaffinity labeling studies of the rat renal sodium bile salt cotransport system.
The uptake of a photolabile taurocholate derivative, (7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-aminoethanesulfonate, 7,7-azo-TC, into rat renal brush-border membrane vesicles was stimulated by Na+ and inhibited by taurocholate indicating an interaction with the Na+/bile salt cotransport system. Irradiation of membrane vesicles in the presence of 7,7-azo-TC inhibited Na+-dependent taurocholate uptake irreversibly. Photoaffinity labeling with [3H]7,7-azo-TC resulted in a predominant incorporation of radioactivity into a polypeptide with apparent molecular weight of 99,000. These results suggest that the proteins involved in Na+/bile salt cotransport are similar in renal and ileal brush-border membranes, but differ from those in hepatocytes.


Proinflammatory liver and antiinflammatory intestinal mediators involved in portal hypertensive rats.
Proinflammatory (TNF-alpha , IL-1beta, and NO) and antiinflammatory (IL-10, CO) levels were assayed in serum, liver, and small bowel in order to verify a hypothetic inflammatory etiopathogeny of portal hypertension that could be the cause of its evolutive heterogeneity. Male Wistar rats were divided into one control group (n=11) and one group with a triple stenosing ligation of the portal vein (n=23) after 28 days of evolution. In one subgroup of portal hypertensive rats, portal pressure, collateral venous circulation, mesenteric vasculopathy, and liver and spleen weights were determined. In the remaining rats with portal hypertension TNF-alpha, IL-1beta, and IL-10 were quantified in liver and ileum by enzyme-linked immunosorbent assay. NO synthase activity was studied in liver and ileum. CO and NO were measured in portal and systemic blood by spectrophotometry and Griess reaction, respectively. Portal hypertensive rats with mayor spleen weight show hepatomegaly and mayor development of collateral circulation. Ileum release of IL-10 (0.30 +/- 0.12 versus 0.14 +/- 0.02 pmol/mg protein; P< .01) is associated with a liver production of both proinflammatory mediators (TNF-alpha: 2 +/- 0.21 versus 1.32 +/- 0.60 pmol/mg protein; P< .05, IL-1beta: 19.17 +/- 2.87 versus 5.96 +/- 1.84 pmol/mg protein; P=.005, and NO: 132.10 +/- 34.72 versus 61.05 +/- 8.30 nmol/mL; P=.005) and an antiinflammatory mediator (CO: 6.49 +/- 2.99 versus 3.03 +/- 1.59 pmol/mL; P=.005). In short-term prehepatic portal hypertension a gut-liver inflammatory loop, which could be fundamental in the regulation both of the portal pressure and of its complications, could be proposed.


Activation of AMP-activated protein kinase by kainic acid mediates brain-derived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells.
AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis. Kainic acid (KA), a prototype excitotoxin is known to induce brain-derived neurotrophic factor (BDNF) in brain. In this study, we examined the role of AMPK in KA-induced BDNF expression in C6 glioma cells. We showed that KA and KA receptor agonist induced activation of AMPK and KA-induced AMPK activation was blocked by inhibition of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) beta. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPKalpha1 blocked KA-induced BDNF mRNA and protein expression. Inhibition of AMPK blocked KA-induced phosphorylation of CaMKII and I kappaB kinase (IKK) in C6 cells. Finally, we showed that inhibition of AMPK reduced DNA binding and transcriptional activation of nuclear factor-kappaB (NF-kappaB) in KA-treated cells. These results suggest that AMPK mediates KA-induced BDNF expression by regulating NF-kappaB activation.


A quantitative immunocytochemical method for the measurement of islet cell cytoplasmic antibodies.
A quantitative immunocytochemical method for the measurement of islet cell cytoplasmic antibodies has been developed. The method employs human or rat pancreas, a protein A-peroxidase/diaminobenzidine secondary antibody system and an independent measurement of islet total and exocrine mean integrated absorbance by scanning microdensitometry. Specific islet cell cytoplasmic antibody binding (islet total-exocrine mean integrated absorbance) was dependent on serum dilution and substrate reaction time. The detection limit was approximately 5 JDF units. Specific islet cell cytoplasmic antibody binding values with human and rat pancreas were similar. Specific islet cell cytoplasmic antibody binding (human pancreas) was greater (p less than 0.001) in sera from patients with newly diagnosed insulin dependent diabetes mellitus (0.119 +/- 0.086, n = 29) compared to normal sera (0.003 +/- 0.008, n = 29). Thus, the method has been validated and may be useful for measuring the blocking effect of potential antigens on specific islet cell cytoplasmic antibody.


Body mass index and weight change are associated with mortality in chronic kidney disease: A retrospective cohort study using a Japanese medical claims database.
This study aimed to investigate body mass index (BMI) and rate of weight change associated with adverse outcomes in Asian patients with chronic kidney disease. A retrospective cohort study was performed between April 2014 and June 2022 using the administrative claims database compiled by the Japan Medical Data Center. Patients were defined as individuals with comorbidities with chronic kidney disease stages 3 to 5 on admission and were aged ≥40 y with BMI at admission and BMI information from a previous admission 3 to 12 mo earlier. Restricted cubic spline analysis and thin-plate smoothed spline analysis were performed. A total of 10 802 individuals were analyzed. The mean age was 74.6 ± 11.3 y, number of men was 7175 (66.4%), and 2115 (19.6%) deaths were recorded. Smoothed splines for BMI found that low BMI was associated with high hazard ratio (HR) (BMI = 18.5 kg/m2; HR = 1.3 [1.2-1.4]). Smoothed splines of weight change found higher HR with increasing rate of weight change for both weight gain and loss (weight change rate = -10%; HR = 1.4 [1.3-1.5]; weight change rate = 10%; HR = 1.2 [1.1-1.3]). In thin-plate smoothed spline analysis, the U-curve had a higher odds ratio as BMI decreased in patients with or without dialysis and as the degree of weight change increased. We found trends in BMI and rate of weight change associated with mortality in Asian patients with chronic kidney disease.


Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP).
The optimal treatment of older patients (>65 years) with acute myeloid leukemia (AML) remains challenging in daily clinical practice; a choice has to be made between intensive chemotherapy and best supportive care. To guide physicians, several prognostic factors have been identified and risk scores developed. Recently, the DNA methyltransferase inhibitor azacitidine has become available for use in MDS and AML patients with up to 30% bone marrow blasts. However, limited data are available on the outcome of older unfit AML patients, regardless of their bone marrow blast count. We retrospectively analyzed the outcome of 90 newly diagnosed older unfit AML patients in 9 Institutions from the Apulia Region (REP). Responder patients (evaluation performed after 4 cycles of treatment even in cases of primary failure) showed a better overall survival than non responders (23 vs 6 months, p<.001). ECOG PS≥2 seems to be correlated with OS in multivariate analysis, while neither primary treatment failure (documented after 2 cycles) nor bone marrow blast count were correlated with a worse overall survival either at univariate (22 vs 29 months, p=.ns; 16 vs 19 months, p=.ns) or multivariate analysis. Overall, the results of our retrospective analysis seem to confirm the efficacy of AZA treatment for this unfit AML patients setting, in terms of both CR and OS, regardless of the bone marrow blasts count, while primary treatment failure should not lead to a discontinuation of treatment.


Demilune cells of the cat submandibular gland; an unlikely source of kallikrein.
The functional significance of kallikrein in the salivary gland remains unclear partially because of uncertainty over its precise cellular localization. Kallikrein was thought to originate in acinar cells, until recent evidence from cat and rat localized it primarily to the ducts. The possibility that salivary kallikrein may also be located in demilune cells was investigated in this study. - The total kallikrein content of cat submandibular glands was found to be substantially reduced by sampathetic nerve stimulation; whereas parasympathetic stimulation had no significant effect. These biochemical findings did not correlate with morphological studies that revealed almost complete depletion of the demilune cells secretory granules after stimulation of either division of the autonomic nerve supply. This lack of correlation makes it unlikely that kallikrein is present in the demilune cell secretory granules.


Electrolytic partial fluorination of organic compounds. 79. Anodic fluorination of spiropyrazoline-5,3'-chroman-4-ones and thiochromanone analogues. A route to aroyl fluoride derivatives.
[reaction: see text] Anodic fluorination of spiropyrazole-5,3'-chroman-4-ones and their thiochromanone analogues in dimethoxyethane containing Et4NF x 4HF resulted in ring opening of spiroheterocycles, which led to the formation of (5-pyrazolyl)methyl o-carbomethoxyphenyl ethers and their thioether analogues via benzoyl fluoride derivatives.


Thomas Henry Huxley's developmental view of the cell.
In 1853, the British physiologist Thomas Henry Huxley roundly criticized German cell theory. Historians have had difficulty explaining how such a 'progressive' biologist could have rejected cellular autonomy and the central role of the nucleus in cell life. The key to Huxley's thinking is provided by understanding his 'epigenetic' philosophy of biology.


Carbetocin versus oxytocin following vaginal and Cesarean delivery: a before-after study.
A nationwide shortage of oxytocin in Canada resulted in a temporary switch from oxytocin to carbetocin for all postpartum women at our institution. This change offered a unique opportunity to conduct a pragmatic comparative assessment of the efficacy of carbetocin and oxytocin. In a retrospective before-after study, we reviewed the medical records from 641 women in the carbetocin group and 752 women in the oxytocin group . The standard carbetocin dosing was 100 µg iv following vaginal and intrapartum Cesarean delivery, while for elective Cesarean delivery it was 50 µg, with an additional 50 µg if required. The standard oxytocin dosing was 5 IU iv followed by 2.4 IU·hr-1 for four to six hours after vaginal delivery, while for Cesarean delivery it was 1-3 IU iv, three minutes apart, up to 10 IU if required, followed by the same maintenance. In both modalities of delivery, if uterine tone was suboptimal, the maintenance dose of oxytocin could be increased to 4.8 IU·hr-1. In both groups, additional uterotonics were used as required. The primary outcome was the need for additional uterotonics. Secondary outcomes included estimated and calculated blood loss, the occurrence of postpartum hemorrhage, and the need for blood transfusion. The incidence of additional uterotonic use was not different between the carbetocin and oxytocin groups (12.0% vs 8.8%; P = 0.05; odds ratio, 1.39; 95% confidence interval, 0.97 to 2.00). The incidence of postpartum hemorrhage was higher in the carbetocin group than in the oxytocin group (10.3% vs 6.6%; P = 0.01). Blood transfusion was more common in the carbetocin group (1.4% vs 0.3%; P = 0.02). There was no difference in the use of additional uterotonics when carbetocin or oxytocin were used in a cohort of women undergoing vaginal deliveries and both elective and emergency Cesarean deliveries.


Outcome of non-visualization of fetal gallbladder on second-trimester ultrasound: cohort study and systematic review of literature.
To investigate the ultrasound characteristics and outcome of fetuses with non-visualization of the fetal gallbladder (NVFGB) followed in our tertiary university hospital, and to provide a comprehensive review of the literature on prenatal findings and outcome of NVFGB. NVFGB was defined as non-visualization of the gallbladder on two targeted ultrasound examinations performed within a 1-week period. First, we reviewed the medical records of NVFGB cases managed in our center over a 9-year period. Then, we performed a systematic review of the literature to identify studies on NVFGB. The incidence of chromosomal anomalies, later visualization of the gallbladder, gallbladder agenesis, cystic fibrosis and biliary atresia was assessed in fetuses with isolated and non-isolated NVFGB. The role of hepatic enzyme measurements in the diagnosis of cystic fibrosis and biliary atresia in fetuses with NVFGB was also reviewed. Sixteen cases of NVFGB were followed in our center, in 10 (62.5%) of which it was an isolated finding. The incidence of biliary atresia was 12.5% and that of gallbladder agenesis was 12.5%, while no case of cystic fibrosis was reported. The gallbladder was visualized later in pregnancy or postnatally in 43.8% and 25.0% of cases, respectively. A total of seven studies, including our cohort, involving a total of 280 NVFGB cases, met the inclusion criteria for the systematic review. Overall, 20.5% of fetuses had an associated ultrasound anomaly, and the incidence of chromosomal anomaly in this group was 20.4%. In cases with isolated NVFGB, the incidence of chromosomal anomaly was 1.9%. In fetuses with normal karyotype and isolated NVFGB, the gallbladder was later visualized in 70.4% of cases, while the incidence of gallbladder agenesis, cystic fibrosis and biliary atresia was 25.2%, 3.1% and 4.8%, respectively. In fetuses with non-isolated NVFGB, the incidence of cystic fibrosis and biliary atresia was 23.1% and 18.2%, respectively. The negative predictive value of amniotic fluid enzyme levels for the prediction of severe disease (including biliary atresia or cystic fibrosis) ranged between 94% and 100% when evaluated before 22 weeks' gestation, and dropped to 88% after 22 weeks. In cases with persistent NVFGB, the risk of a severe postnatal condition should be considered. A detailed ultrasound scan should be offered and parents tested for cystic fibrosis gene mutation. An invasive procedure for karyotyping and measurement of liver enzyme concentrations before 22 weeks constitutes a reasonable work-up. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Sibling rivalry in the E2F family.
The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators. The individual E2Fs can be divided into distinct subgroups that act in direct opposition to one another to promote either cellular proliferation or cell-cycle exit and terminal differentiation. What is the underlying molecular basis of this 'push-me-pull-you' regulation, and what are its biological consequences?


Impact of daytime spectral tuning on cognitive function.
Light at night can improve alertness and cognition. Exposure to daytime light, however, has yielded less conclusive results. In addition to direct effects, daytime light may also mitigate the impact of nocturnal light exposure on alertness. To examine the impact of daytime lighting on daytime cognitive performance, and evening alertness, we studied nine healthy individuals using a within subject crossover design. On four visits, participants were exposed to one of four lighting conditions for 10 h (dim fluorescent, room fluorescent, broad-spectrum LED, standard white LED; the latter three conditions were matched for 100 lx) followed by an exposure to bright evening light. Cognitive performance, subjective and objective measures of alertness were regularly obtained. While daytime alertness was not impacted by light exposure, the broad-spectrum LED light improved several aspects of daytime cognition. The impact of evening light on alertness was not mitigated by the pre-exposure to different daytime lighting conditions. Results suggest that daytime exposure to white light with high melanopic efficacy has the potential to improve daytime cognitive function and that such improvements are likely to be direct rather than a consequence of light-induced changes in alertness.


Conservative management of temporomandibular disorders: a posttreatment comparison between patients from a university clinic and from private practice.
Long-term (1 to 7.5 years) follow-up evaluations of 110 adult patients who were seen for diagnosis and treatment of symptoms related to myofascial problems (MP), internal derangement (ID), or both were conducted by means of telephone interview. One half of the patients were seen at the Northwestern University Dental School TMJ Clinic, while the other half were seen in the private office of one author (H. T. P.). The purpose of this study was to evaluate patient response to conservative therapy combined with advice about self-management, as compared with the response to advice only. Further, we desired to compare treatment outcomes among (1) diagnostic categories ID, MP, and ID plus MP, (2) clinic patients and private patients, and (3) patients with acute disease and those with chronic disease. Chronic disease was identified as that in which pretreatment symptoms had persisted for more than 4 months. The ridit analysis was used to assess differences in outcomes for patients in the three diagnostic categories and for clinic patients compared with private patients. The results revealed no significant differences. There was a trend for patients with acute conditions to improve more than those with chronic problems; however, further research is needed to determine whether a correlation exists between symptom duration and treatment outcome. At the time of the follow-up evaluation, 88% of all patients reported substantial or total improvement in their symptoms of pain and dysfunction. Therefore, conservative therapy, including advice about self-management, was found to be both adequate and appropriate for most of these patients.


Alterations of choroidal circulation and vascular morphology in a patient with chronic myeloid leukemia before and after chemotherapy.
Chronic myeloid leukemia (CML) is known to cause leukemic retinopathy due to leukemia cell invasion into the choroid; however, details of the circulatory dynamics and morphological changes in the choroid are unknown. The aim of this study was to present a case of leukemic retinopathy and examine choroidal circulatory and structural analyses using laser speckle flowgraphy (LSFG) and optical coherence tomography with a binarization method, respectively. A 15-year-old male diagnosed with CML complained of blurred vision in his right eye. He was ophthalmologically diagnosed with leukemic retinopathy due to retinal hemorrhage in both eyes. Tyrosine kinase inhibitors achieved complete cytogenetic remission and resolution of retinal hemorrhages at 6 months after treatment. After the treatment, the best-corrected visual acuity had recovered from 0.1 to 1.2 oculus dexter (OD) and remained at 1.5 oculus sinister (OS). The rate of change in macular blood flow assessed by the mean blur rate on LSFG was 18.3% increase OD and 25.2% decrease OS 19 months after treatment. The central choroidal thickness showed 0.4 and 3.1% reductions OD and OS, respectively. The binarization technique demonstrated that the rate of luminal areas in choroidal areas exhibited 3.2% increase OD but 4.8% decrease OS. Choroidal blood flow improved OD after treatment for CML, while it deteriorated OS, together with choroidal thinning due to reduction of luminal areas. The degrees of leukemia cell invasion into the choroidal tissue and tissue destruction might be different between the eyes in this case.


Leptin as a marker for severity and prognosis of aneurysmal subarachnoid hemorrhage.
Leptin has been identified as a plasma marker for outcomes in traumatic brain injury and intracerebral hemorrhage. We further investigated whether leptin might serve as a marker for severity and prognosis in aneurysmal subarachnoid hemorrhage. One hundred and eight consecutive patients and 108 sex and age - matched healthy subjects were recruited. Plasma leptin levels were measured by enzyme-linked immunosorbent assay. Clinical severity was assessed using World Federation of Neurological Surgeons score and Fisher score. Mortality and poor long-term outcome (Glasgow outcome scale scores of 1-3) at 6 months were recorded. Plasma leptin levels on admission were substantially higher in patients than in healthy controls, and were significantly associated with the clinical severity. There was also a significant association between leptin levels and clinical outcomes at 6 months in multivariate logistic regression analysis. Using receiver operating characteristic curves, we calculated areas under the curve for clinical outcomes at 6 months. The predictive performance of leptin was similar to, but did not obviously improve those of World Federation of Neurological Surgeons score and Fisher score. Thus, leptin may indicate clinical severity of the initial bleeding and also have prognostic value for clinical outcomes in aneurysmal subarachnoid hemorrhage and may therefore help in guiding treatment decisions in the setting of aneurysmal subarachnoid hemorrhage.


Laparoscopic adjustable silicone gastric banding for morbid obesity: results and complications in 715 patients.
Laparoscopic adjustable silicone gastric banding (LASGB) was used as the initial bariatric procedure for more than 36 months. The efficacy and safety of LASGB were studied. Patients were followed up prospectively in a multidisciplinary center for the perioperative and long-term courses, and for complications. Between November 1996 and May 1999, 715 patients underwent surgery. The mean age was 34.6 years (range, 16-72) years, and the mean body mass index (BMI) was 43.1 kg/m2 (range, 35-66 kg/m2). The mean operative time was 78 min (range, 36-165 min), and the postoperative hospitalization time was 1.2 days (range, 1-8 days). There were six intraoperative complications (0.8%), eight early postoperative complications (1.1%), and no deaths. For follow-up evaluation, 614 patients (86%) were available. Late complications included band slippage or pouch dilation in 53 patients (7.4%), band erosion in 3 patients, and port complications in 18 patients. In 57(7.9%) patients, 69 major reoperations were performed. In patients with a follow-up period longer than 24 months, the average BMI dropped from 43.3 kg/m2 (range, 35-66 kg/m2) to 32.1 kg/m2 (range, 21-45 kg/m2). Laparoscopic adjustable silicone gastric banding is safe, with a lower complication rate than any other bariatric procedure. Most reoperations can be performed laparoscopically with low morbidity and short hospitalizations. On the basis of intermediate-term follow-up evaluation, it is an effective procedure for weight-reducing purposes.


Neurogenesis and neuron regeneration in the olfactory system of mammals. II. Degeneration and reconstitution of the olfactory sensory neurons after axotomy.
This report describes the retrograde degeneration affecting olfactory sensory neurons of rats after severance of their axons and illustrates the reconstitution of new neurons originating from stem cells located at the base of the olfactory neuroepithelium. Degeneration of the mature, axotomized neurons, signalled by an increased electron density of their cytoplasmic matrix and by the appearance of lipofuscin-like granules, can be detected in the neuroepithelium as early as 24 h after surgery and becomes conspicuous between the second and the third day. Degenerating neurons can be observed in decreasing number up to the tenth post-operative day. They are removed by macrophages which invade the epithelium. The reconstitution of new neurons begins to occur after eight days, when the stem cells undergo vigorous mitotic activity and differentiate into neurons. The morphology of the reconstituted neurons has been described in detail at different stages of their maturation. After 30 days, the olfactory epithelium appears similar to controls. On the basis of both morphological (in rats) and autoradiographic ( in mice) observations, the basal cells have been recognized as stem cells of the olfactory neurons.


Deconstructing the electron transfer chain in a complex molybdoenzyme: Assimilatory nitrate reductase from Neurospora crassa.
Nitrate reductase (NR) from the fungus Neurospora crassa is a complex homodimeric metallo-flavoenzyme, where each protomer contains three distinct domains; the catalytically active terminal molybdopterin cofactor, a central heme-containing domain, and an FAD domain which binds with the natural electron donor NADPH. Here, we demonstrate the catalytic voltammetry of variants of N. crassa NRs on a modified Au electrode with the electrochemically reduced forms of benzyl viologen (BV2+) and anthraquinone sulfonate (AQS-) acting as artificial electron donors. The biopolymer chitosan used to entrap NR on the electrode non-covalently and the enzyme film was both stable and highly active. Electrochemistry was conducted on two distinct forms; one lacking the FAD cofactor and the other lacking both the FAD and heme cofactors. While both enzymes showed catalytic nitrate reductase activity, removal of the heme cofactor resulted in a more significant effect on the rate of nitrate reduction. Electrochemical simulation was carried out to enable kinetic characterisation of both the NR:nitrate and NR:mediator reactions.


Immunological differences among the cholera/coli family of enterotoxins.
Pure enterotoxins from two strains of Vibrio cholerae and choleragen-related heat-labile enterotoxins (LTs) from strains of Escherichia coli of human and porcine origin were examined by Ouchterlony-type immunodiffusion assays and by neutralization tests in Y-1 adrenal cells using specific and immunopurified antisera. In accordance with previous findings, the results indicated that each of the toxins shared antigens with each of the others and that each, in addition, possessed unique antigenic determinants. The present study, however, indicates further that enterotoxin-type specific antibodies, in some instances, account for a major portion of the neutralizing activity. The full extent and importance of the antigenic drift in the cholera/coli family of ADP-ribosylating, adenylate cyclase-activating, heat-labile enterotoxins remains to be determined. The results will be pertinent to efforts to develop broad-spectrum antitoxic immunity as well as in the development of methods for the rapid detection and identification of enterotoxigenic strains.


The distribution of axons according to diameter in the optic nerve and optic tract of the rat.
The distribution of axons according to diameter was examined in the optic nerve and optic tract of adult hooded rats. Observations were made on semithin sections, and measurements of axonal diameters were made on electron micrographs taken from various locations across thin sections through the optic nerve and tract. The distribution of axons by size differs markedly in the optic nerve and tract. Coarse (greater than 2 microns) and fine (less than or equal to 2 microns) axons are distributed throughout all regions of the optic nerve. In the optic tract, in contrast, coarse axons are especially dense dorsally, at the deep border of the tract, while they are absent ventrally, subjacent to the pial surface. No regions of the optic nerve contain densities of coarse axons as high as the deep nor as low as the superficial extremes of the optic tract. Nevertheless, even at the deep (dorsal) border of the optic tract, the coarse axons make up only a small minority (roughly 15%) of the total number of axons in that region. The axons 2 microns or smaller may be divisible into two overlapping, fine and intermediate, diameter classes, that are partially segregated within the optic tract, but not in the optic nerve: the distributions of axon diameters smaller than 2 microns are skewed to distinctly smaller diameters at the dorsal and ventral extremes of the optic tract, while in between, at mid-positions along the deep-to-superficial axis of the optic tract, the axon size distributions contain many more axons greater than 1 micron in diameter. These different axon diameter groups may arise from the morphologically distinct retinal ganglion cell types, and may underlie the components of the trimodal compound axon potential seen in the rat's primary optic pathway. Their partial segregation within the tract anticipates the partial segregation of their terminal arborizations within the laminae of the dorsal lateral geniculate nucleus. The rearrangement of axons into a partial segregation by size within the optic tract may indicate a chronology of axonal arrival during early development, proximity to the pial surface being an index of recency of arrival. As axonal outgrowth and neurogenesis appear to be directly related within the retinal ganglion cell population in mammals, the relative birthdates of the retinal ganglion cell types giving rise to the axon diameter classes in the rat may be inferred from the present results.


I got it from my mother: Inter-nest variation of mercury concentration in neonate Smooth-fronted Caiman (Paleosuchus trigonatus) suggests maternal transfer and possible phenotypical effects.
The deleterious effects of mercury (Hg) contamination are well documented in humans and wildlife. Chronic exposure via diet and maternal transfer are two pathways which increase the toxicological risk for wild populations. However, few studies examined the physiological impact of Hg in crocodilians. We investigated the Hg contamination in neonate Smooth-fronted Caimans, Paleosuchus trigonatus, and the use of keratinized tissues and blood to evaluate maternal transfer. Between November 2017 and February 2020, we sampled 38 neonates from 4 distinct nests. Mercury concentration was measured in claws, scutes and total blood. Highest Hg concentrations were found in claws. Strong inter-nest variations (Hg ranging from 0.17 ± 0.02 to 0.66 ± 0.07 μg.g-1 dw) presumably reflect maternal transfer. Reduced body size in neonates characterized by elevated Hg concentrations suggests an influence of Hg during embryonic development. We emphasize the use of claws as an alternative to egg collection to investigate maternal transfer in crocodilians. Our results demonstrated the need of further investigation of the impact of Hg contamination in the first life stages of crocodilians.


Intimate partner violence and lower relationship quality are associated with faster biological aging.
The characteristics of people's relationships have relevance to health-high quality romantic relationships are associated with improved health whereas intimate partner violence is associated with poorer health. Recently, increased attention has been focused on the biological processes underpinning these associations. A geroscience approach-examining whether close relationship characteristics are associated with biological aging-would complement previous research focused on individual disease pathways. This study used participants from the Dunedin Study (N = 974) to investigate relationship characteristics and biological aging across almost 20 years, from age 26 to 45. Being involved in romantic relationships was associated with slower biological aging, β = -0.12, p < .001. This difference represented 2.9 years of aging over the two decades. Greater relationship quality was also associated with slower biological aging, β = -0.19, p < .001, whereas higher levels of partner violence were associated with faster biological aging, β = 0.25, p < .001. A 1 SD difference in these characteristics was associated with a difference of 1.0 and 1.3 years of aging over the two decades, respectively. Secondary analyses suggested that experiencing violence from a partner was more strongly associated with biological aging than perpetrating violence, and that the experience of physical violence was more strongly associated with aging than psychological violence. These findings suggest that the characteristics of romantic relationships have relevance for biological aging in midlife. Interventions designed to increase relationship quality and decrease partner violence could reduce future morbidity and early mortality by slowing people's biological aging. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


The Chinese pine genome and methylome unveil key features of conifer evolution.
Conifers dominate the world's forest ecosystems and are the most widely planted tree species. Their giant and complex genomes present great challenges for assembling a complete reference genome for evolutionary and genomic studies. We present a 25.4-Gb chromosome-level assembly of Chinese pine (Pinus tabuliformis) and revealed that its genome size is mostly attributable to huge intergenic regions and long introns with high transposable element (TE) content. Large genes with long introns exhibited higher expressions levels. Despite a lack of recent whole-genome duplication, 91.2% of genes were duplicated through dispersed duplication, and expanded gene families are mainly related to stress responses, which may underpin conifers' adaptation, particularly in cold and/or arid conditions. The reproductive regulation network is distinct compared with angiosperms. Slow removal of TEs with high-level methylation may have contributed to genomic expansion. This study provides insights into conifer evolution and resources for advancing research on conifer adaptation and development.


Successful treatment of methicillin-resistant Staphylococcus aureus pulmonary infection with linezolid in a patient with cystic fibrosis.
Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of pulmonary infection in patients with cystic fibrosis (CF). Because these organisms are frequently multidrug-resistant, most patients require intravenous therapy with vancomycin. We report on the first case of successful treatment of a pulmonary exacerbation due to MRSA in a CF patient with a new antimicrobial, linezolid. We demonstrated equivalence of intravenous and oral dosing in this patient, suggesting that oral linezolid may be an excellent alternative to intravenous vancomycin for CF patients infected with MRSA.


Important factors in left atrial posterior wall isolation using 28-mm cryoballoon ablation for persistent atrial fibrillation-Block line or isolation area?
Left atrial (LA) roof ablation using the cryoballoon technique, combined with pulmonary vein isolation (PVI), has been reported to be beneficial for ablation therapy in patients with persistent atrial fibrillation (AF). Left posterior wall ablation also results in improved patient outcomes. However, the contribution of these techniques to the success of cryoballoon ablation (CBA) treatment of AF is not known. The present study examined the influence of the roofline block and isolation area on outcomes after CBA. We enrolled 78 patients with persistent AF. LA roof ablation was performed using a 28-mm cryoballoon with a single freezing of 3 minutes at each region (median number of freezes: 4) after PVI. After CBA, bipolar voltage amplitude mapping was performed during sinus rhythm using the NavX mapping system. Patients were divided into two subgroups according to the voltage and activation map: the roof-conduction (n = 46) and roofline-block groups (n = 32). Atrial tachyarrhythmia recurred in 20 patients of the conduction group and 4 patients of the roofline-block group. The rate of 12-month freedom from tachyarrhythmia after a single ablation procedure was 78% (95% confidence interval [CI], 60%-89%) in the roofline-block group and 45% (95% CI, 30%-60%) in the conduction group (P = .048). Cox proportional hazard analysis revealed that the isolated area was not a significant predictor of recurrence (hazard ratio, 0.94; 95% CI, 0.86-1.02; P = .15). Creating a complete roofline block is the major factor predicting the maintenance of sinus rhythm in patients with persistent AF.


Design and antileishmanial activity of amphotericin B-loaded stable ionic amphiphile biovector formulations.
A new delivery system, Ionic Amphiphilic Biovector (ABV), comprised of anionic lipids (dipalmitoyl phosphatidyl glycerol) included in a cationic cross-linked polysaccharide matrix was used as a reservoir for amphotericin B (AmB). Two ABV formulations exhibited an in vitro and in vivo efficacy similar to commercial AmBisome against Leishmania donovani-infected mice. The higher stability of these ABV formulations indicates their potential for further development and applications.


Phylodynamics of classical swine fever virus in Brazil.
The classical swine fever virus is the etiologic agent of one of the diseases with the greatest impact on swine farming worldwide. An extensive area of Brazil is considered free of the disease, but some states in Northeast Brazil have registered outbreaks since 2001. The objective of this study was to analyze the genetic variations of the virus and its spread over time and space. Partial sequences of the viral E2 protein obtained from samples collected during the Brazilian outbreaks were compared with sequences from the GenBank database (NCBI). The results demonstrated the continuous presence of the virus in the state of Ceará, with diffusion to at least two other states. The Brazilian Northeast virus presents specific polymorphisms that separate it from viruses isolated in other countries.


Malignant rhabdoid tumour of the bladder with immunohistochemical and ultrastructural evidence suggesting histiocytic origin.
A malignant rhabdoid tumour of the bladder is reported from a girl aged 6. Detailed immunohistochemical and ultrastructural investigations provide evidence which suggests a histiocytic origin for this controversial neoplasm.


Computed tomographic analysis of brain morphometrics in 30 healthy men, aged 21 to 81 years.
Computed transverse axial tomography (CT) was employed to examine brain morphometrics in 30 healthy men, aged 21 to 81 years. Seven consecutive CT slices 30 to 80 mm above the inferior orbitomeatal line were analyzed. CT numbers in gray and white matter regions were not correlated significantly with age (p greater than 0.05), nor were right/left ratios for derived parameters. The volume of gray matter was correlated negatively with age (p less than 0.05), and the volume of cerebrospinal fluid correlated positively with age, in the seven slices. The volumes of the lateral and third ventricles were elevated in the elderly, and volumes of the thalamus and lenticular nucleus were reduced. The results demonstrate that brain atrophy, evidenced by a loss of gray matter and by dilatation of cerebrospinal fluid spaces, occurs in the healthy elderly, and provide baseline CT-derived brain morphometric data for healthy men in relation to age.


Family contact and the management of medication non-adherence in schizophrenia.
We compare psychiatric management of antipsychotic non-adherence among schizophrenia outpatients with high and low levels of family contact. A national survey was conducted among a random sample of psychiatrists treating schizophrenia, providing data on 310 patients. Patients were stratified by level of family contact. Psychiatrists were more likely to use family interventions to manage non-adherence among patients with high family contact. Psychiatrists were significantly more likely to change antipsychotic dosing in patients with high family contact, though less likely to start depot antipsychotic medications. Family interventions appear to be commonly used in the psychiatric management of medication non-adherence in schizophrenia.


Schizophrenia: One Name, Many Different Manifestations.
Schizophrenia is a disabling condition impacting approximately 1% of the worldwide population. Symptoms include positive symptoms (eg, hallucinations, delusions), negative symptoms (eg, avolition, anhedonia), and cognitive impairment. There are likely many different environmental and pathophysiologic etiologies involving distinct neurotransmitters and neurocircuits. Pharmacologic treatment at present consists of dopamine receptor antagonists, which are reasonably effective at treating positive symptoms, but less effective at treating cognitive and negative symptoms. Nondopaminergic medications targeting alternative receptors are under investigation. Supportive psychosocial treatments can work in tandem with antipsychotic medications and optimize patient care.


Dopaminergic therapy improves upper limb motor performance in aged rhesus monkeys.
The potential of dopaminergic treatments to improve upper limb motor movements was tested in 7 aged rhesus monkeys using L-3,4-dihydroxyphenylalanine (L-dopa) or the selective dopamine uptake inhibitor 1-2(bis[4-fluorophenyl] methoxy]ethyl)-4-(3-phenylpropyl) piperazine hydrochloride (GBR-12909). Six young monkeys were studied for comparison. L-Dopa or GBR-12909 improved upper limb motor performance by up to 40% in the aged animals. At this point their performance was comparable to that of young adults. Dopaminergic therapy could be useful in elderly humans experiencing declines in upper limb motor functions.


Development and Validation of a Nomogram to Predict Recurrence of Primary Hyperhidrosis after CT-guided Percutaneous Radiofrequency Sympathectomy.
To evaluate the recurrence rate of primary hyperhidrosis (PH) after computed tomography (CT)-guided radiofrequency sympathectomy (RFS) and identify risk factors associated with recurrence. A total of 290 patients with PH who underwent CT-guided RFS were included in this retrospective cohort study. The electronic medical record was reviewed for patients' information and procedural parameters. Follow-ups were conducted for recurrence rate, and Hyperhidrosis Disease Severity Scale was used to assess presence or absence of recurrence. Stepwise regression and the least absolute shrinkage and selection operator regression algorithms were used for feature selection. The recurrence rate 1 year after procedure was 17.6%. Male (hazard ratio [HR], 2.35; 95% confidence interval [CI], 1.08-5.15), low postoperative palm or foot temperature (HR, 0.77; 95% CI, 0.60-0.98), high postoperative heart rate (HR, 1.06; 95% CI, 1.02-1.10), low preoperative and postoperative hospital anxiety and depression score difference (HR, 0.59; 95% CI, 0.43-0.80), and the absence of compensatory hyperhidrosis immediately after procedure (HR, 0.46; 95% CI, 0.22-0.98) were established as independent factors affecting prognosis. A nomogram was built accordingly. The C indices of the training and testing sets were 0.773 and 0.659, respectively. Follow-up results showed that the recurrence rate of PH treated with CT-guided RFS was low. This study constructed and validated a nomogram to predict the recurrence of PH 1 year after CT-guided RFS, which is convenient for interventionalists to evaluate accurately the prognosis of patients postoperatively and to identify high-risk patients who need more active treatment.


Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions.
Lupus erythematosus comprises a spectrum of autoimmune diseases that may affect various organs (systemic lupus erythematosus [SLE]) or the skin only (cutaneous lupus erythematosus [CLE]). Typical combinations of clinical, histological and serological findings define clinical subtypes of CLE, yet there is high interindividual variation. Skin lesions arise in the course of triggers such as ultraviolet (UV) light exposure, smoking or drugs; keratinocytes, cytotoxic T cells and plasmacytoid dendritic cells (pDCs) establish a self-perpetuating interplay between the innate and adaptive immune system that is pivotal for the pathogenesis of CLE. Therefore, treatment relies on avoidance of triggers and UV protection, topical therapies (glucocorticosteroids, calcineurin inhibitors) and rather unspecific immunosuppressive or immunomodulatory drugs. Yet, the advent of licensed targeted therapies for SLE might also open new perspectives in the management of CLE. The heterogeneity of CLE might be attributable to individual variables and we speculate that the prevailing inflammatory signature defined by either T cells, B cells, pDCs, a strong lesional type I interferon (IFN) response, or combinations of the above might be suitable to predict therapeutic response to targeted treatment. Therefore, pretherapeutic histological assessment of the inflammatory infiltrate could stratify patients with refractory CLE for T-cell-directed therapies (e.g. dapirolizumab pegol), B-cell-directed therapies (e.g. belimumab), pDC-directed therapies (e.g. litifilimab) or IFN-directed therapies (e.g. anifrolumab). Moreover, Janus kinase (JAK) and spleen tyrosine kinase (SYK) inhibitors might broaden the therapeutic armamentarium in the near future. A close interdisciplinary exchange with rheumatologists and nephrologists is mandatory for optimal treatment of lupus patients to define the best therapeutic strategy.


Stockout risk analysis and minimization applied to hospital pharmacy management.
To determine how many dispensary drugs should be in the safety stock in a tertiary hospital in accordance with the risk level and the number of days that the hospital is able to withstand a stockout. We statistically analysed the infliximab order recorded over a period of 120 days. This drug is relevant for this study as it is costly and is immediately supplied to the clinic. Using the data records for purchasing and dispensing in our department, we created a table to compare the level of risk assumed with the number of units in stock and the number of days that the safety stock should last. In addition, we calculated how much stock there should be in accordance with different heuristic rules used by pharmacy departments. In the period being studied, the daily order was 11.4±14.8 units of infliximab. Using the methodology proposed, we discovered that there should be 79 units in the safety stock. Other hospital rules determine values of 47 and 119 units. The method proposed allows us to discover the risk level that is assumed when selecting the safety stock. Therefore, we are able to design a safety stock policy consistent with the risk level adopted. Under certain assumptions the safety stock quota provided by this method could be reduced. Lastly, there is a notable difference between the safety stock values suggested by different rules, as it has been shown in this article.


Pharmacology of Aesthetic Medicines.
The realm of aesthetic medicine is broad, and there are countless medications and topical agents used in the practice of aesthetic medicine. The most commonly used injectable medicines include botulinum toxin for mimetic lines and hyaluronic acid fillers for deeper facial rhytids and volume rejuvenation. Topical aesthetic medicines are useful adjuncts for facial rejuvenation and commonly include tretinoin, hydroquinone, growth factors, and vitamin C, as well as a wide range of chemical peels.


Cytokine concentrations and regulatory T cells in living donor and deceased donor liver transplant recipients.
Outcomes of pediatric liver transplantation have constantly improved in the last decade. Living-related liver transplantation does not seem to improve long-term outcomes following liver transplantation, but few studies have evaluated immunological parameters of the alloimmune response after living vs. deceased donor organ transplantation. We analyzed numbers of regulatory T cells, lymphocyte subsets, and serum cytokine concentrations in 12 pediatric recipients of living-related liver transplants and in 28 pediatric recipients of deceased donor organs during their annual follow-ups. Transplant recipients who underwent living donor organ transplantation had significantly higher numbers of regulatory T cells and IL-4 serum concentrations than recipients of deceased donor organs; both of these factors are associated with beneficial outcomes and transplantation tolerance. Living-related liver transplantation may have potentially beneficial immunological aspects, although long-term outcomes do not seem to be better in recipients of living donor organs than in recipients of deceased donor organs. Further studies are needed to compare immunological aspects of the two transplant procedures.


Mathematical modeling of cytotoxicity of metal oxide nanoparticles using the index of ideality correlation criteria.
Several types of metal oxide nanoparticles (MO-NPs) are often utilized as one of the novel class of materials in the pharmaceutical industry and human health. The wide use of MO-NPs forces an enhanced understanding of their potential impact on human health and the environment. The research aims to investigate and develop a nano-QFAR (nano-quantitative feature activity relationship) model applying the quasi-SMILES such as cell line, assay, time exposition, concentration, nanoparticles size and metal oxide type for prediction of cell viability (%) of MO-NPs. The total set of 83 quasi-SMILES of MO-NPs divided into training, validation and test sets randomly three times. The statistical model results based on the balance of correlation target function (TF1) and index of ideality correlation target function (TF2) and the Monte Carlo optimization were compared. The comparison of two target function results indicated that TF2 improves the predictability of models. The significance of various eclectic features of both increase and decrease of cell viability (%) is provided. Mechanistic interpretation of significant factors for the model are proposed as well. The sufficient statistical quality of three nano-QFAR models based on TF2 reveals that the developed models can be efficiency for predictions of the cell viability (%) of MO-NPs.


Toxicity of extended courses of linezolid: results of an Infectious Diseases Society of America Emerging Infections Network survey.
Since linezolid was licensed, rare-but-serious adverse events caused by inhibition of mitochondrial protein synthesis have been identified. These events may be more common when the drug is used longer than 28 days, which is the treatment length currently approved by the US Food and Drug Administration. The purpose of this study was to determine how often longer courses of linezolid are prescribed and the nature and relative frequency of adverse events associated with longer courses. Most of the 460 infectious diseases physician respondents had prescribed extended course linezolid (greater than 28 days) at least once, and they reported that 74% of these patients were able to complete the extended course. Hematologic toxicity was the most common adverse event. Peripheral neuropathy and serotonin syndrome (with serotonin reuptake inhibitor use) were encountered more frequently than lactic acidosis. Close monitoring for signs and symptoms of these adverse events should be considered for patients receiving long-term therapy.


Modulation of leukocyte adhesion in rat mesenteric venules by aspirin and salicylate.
Erythrocyte velocity, vessel diameter, leukocyte rolling velocity, and number of adherent and emigrated leukocytes were measured in postcapillary venules both before and during superfusion of rat mesentery with either aspirin or sodium salicylate. In some experiments, animals were treated with either a leukotriene (LT)-synthesis inhibitor (L-663,536), an LTD4 antagonist (MK-571), an LTB4 antagonist (SC-41930), misoprostol, or prostaglandin (PG) I2, then the aspirin protocol was repeated. Superfusion of aspirin but not sodium salicylate resulted in increased leukocyte adherence and a reduced leukocyte rolling velocity but did not affect leukocyte emigration. Aspirin-induced leukocyte adhesion was effectively prevented by the LT-synthesis inhibitor and LTB4 antagonist but not by the LTD4 antagonist. Misoprostol and PGI2 also prevented the aspirin-induced adhesion responses. Superfusion of the mesentery with either platelet-activating factor (PAF) or LTB4 enhanced leukocyte adherence and emigration while reducing leukocyte rolling velocity. Sodium salicylate prevented all of the adhesion responses elicited by LTB4. Although salicylate did not affect the PAF-induced leukocyte adherence and rolling responses, it completely prevented the increased leukocyte emigration. These results indicate that aspirin promotes, whereas sodium salicylate inhibits, leukocyte-endothelial cell adhesive interactions at therapeutically relevant concentrations.


In vitro propagation and cell cultures of memory tonic herb Evolvulus alsinoides: a best source for elicited production of scopoletin.
Evolvulus alsinoides L. is used for preparation of 'Shankhapushpi', an important popular ayurvedic drug that contributes considerably to the improvement of memory power. The improvement is attributed to the presence of furanocoumarin scopoletin, a metabolite with a wide range of biological activities. This report describes, for the first time, an in vitro culture system for propagation and enhanced production of scopoletin. Different concentrations of auxins and cytokinins individually and in combination were used in Murashige and Skoog (MS) medium to induce shoot regeneration in cotyledonary nodal explants and callus formation in leaf explants. The best response was achieved in MS medium fortified with 5.0 μM 6-benzyladenine (BA) in which 96 % of cultures produced 7.6 ± 0.6 shoots per explant. Regenerated shoots were rooted on MS medium with 5.0 μM indole-3-acetic acid (IAA). Plantlets were successfully acclimatized and established in soil. MS medium fortified with 10 μM BA + 5.0 μM IAA showed maximum growth and accumulation of scopoletin in cell cultures. Cell cultures could be maintained over 24 months. The influences of auxins, cytokinins, organic acids, amino acids, and fungal-derived elicitors on production of scopoletin were studied. Presence of either L-arginine, sodium pyruvate, or yeast extract highly promoted scopoletin production as compared with control and achieved 75.02-, 72.13-, and 57.98-fold higher accumulation, respectively. The results presented herein have laid solid foundation for large-scale production of scopoletin and further investigation of its purification and utilization as a novel pharmaceutical drug.


Procedures for evaluating the dyadic adjustment of drug-abusing patients and their intimate partners. A multimethod assessment approach.
This article describes a basic multimethod relationship assessment procedure used by the authors in their recent investigations to evaluate the relationship adjustment of married or cohabiting drug-abusing patients and their intimate partners. The components of the assessment include (a) semistructured clinical interviewing; (b) a battery of paper-and-pencil self-report inventories; and (c) observations of partners engaging in a conflict resolution discussion, coded using a standardized rating system. The essential features of the relationship assessment procedure (i.e., brevity, breadth, depth, and use of psychometrically sound measures) would allow this method to be used routinely in nonresearch settings that treat substance-abusing patients. A case example is provided to illustrate the use of these relationship assessment methods with a drug-abusing couple.