Successful surgical management of rupture of the left ventricle and interventricular septum due to blunt chest trauma. Case report.
In a 35-year-old man blunt chest trauma caused rupture of the free wall of the left ventricle and the interventricular septum. Emergency pulse Doppler-2D echocardiography confirmed the clinical suspicion and immediate surgical repair was successfully undertaken. This appears to be the first reported case of survival after surgery for such combined cardiac rupture.


Formulation and delivery solutions for the next generation biotherapeutics.
In 2018 I was appointed full professor of Pharmaceutical Biotechnology & Delivery at the Pharmaceutics division of the department of Pharmaceutical Sciences at Utrecht University, The Netherlands. In this contribution to the Orations - New Horizons of the Journal of Controlled Release I will introduce my research group (see also www.uu.nl/pharmaceutics) and will highlight my current and future research projects. In coming years the focus of my research will be on the administration of biotherapeutics, aiming to control their fate from the site of injection to the site of action. I will discuss issues related to formulation of biotherapeutics into nanomedicines (NMs), intracellular delivery of nucleic acids as well as protein therapeutics, and targeted delivery of biotherapeutics beyond the liver. In addition, I will provide a forward view on how current developments in the drug delivery and gene therapy field may result in sustainable and cost-effective dosing regimens for biotherapeutics.


The 23rd Scientific Conference of the Society on Neuroimmune Pharmacology.
The 23rd Scientific Conference of the Society on Neuroimmune Pharmacology (SNIP) will take place in Philadelphia, PA, USA, from March 29 to April 1, 2017. The conference will present a selection of the latest and most advanced research in the intersecting areas of neuroscience, immunology, pharmacology and its translational aspects.


Carcinoma of the cervix in Southwestern American indians: results of a cytologic detection program.
Age-specific detection rates for newly diagnosed in situ and invasive uterine cervical carcinoma were determined in a nine-year cytologic cancer detection program during which 34,700 Southwestern American Indian women and 46,200 medically indigent non-Indian women were screening for cervical cancer. For patients less than 35 years of age, cervical carcino a was found more frequently among Indians and Spanish-American Caucasians than among other Caucasian women. At ages 60 and older, the Indian cervical cancer rate was much higher than that of non-Indians. The detection rate for invasive cervical carcinoma among Indian patients is inversely related to the proportion screened at 30 years of age or older. Although at least 60% of Indian women 20 years old, and older, in the geographic area served by the detection program were screened for cervical cancer during the nine-year period, only 27% of those 50 years or older were screened. The age-related variation in screening percentage, in conjunction with the disproportionately large numbers of younger low-risk women, serves to explain the finding of significant invasive cervical carcinoma in an extensively screened population.


UK NEQAS ICC & ISH Ki-67 Data Reveal Differences in Performance of Primary Antibody Clones.
We examined data from 374 laboratories staining for Ki-67 as part of external quality assessment over 8 runs between 2013 and 2017 (total data sets=2601). One of 5 primary antibodies was used for 94.8% of submissions, with MIB-1 (Agilent Dako) comprising 58.8% of the total. Examining assessment score as a continuous variable showed the 30-9 (Ventana) and K2 (Leica Biosystems) clones were associated with the highest mean scores (17.0; 95% confidence interval, 16.8-17.2 and 16.3; 95% confidence interval, 15.9-16.6, respectively). Stain quality was not significantly different between them. Both were associated with significantly better staining compared with MIB-1 (Agilent Dako), MM1 (Leica Biosystems), and SP6 from various suppliers (P<0.05). Similarly, categorical assessment of "Good" versus "Not good" staining quality showed that the 30-9 and K2 clones were both significantly associated with "Good" staining (both P<0.001). Other methodological parameters were examined for significant primary antibody-specific effects; none were seen for 30-9, K2, or SP6. The MM1 clone was more likely to be associated with good quality staining when it was used with Leica Biosystems sourced antigen retrieval, detection, and platform, all statistically significant at P<0.01. MIB-1 was more likely to be associated with good quality staining results when it was used with Agilent Dako antigen retrieval, detection, and staining platforms (P<0.0001), and less likely at the same significance level when used with Leica Biosystems reagents and equipment. The data presented here show the importance of not just primary antibody choice but also matching that choice to other methodological factors.


Couple/family therapy for posttraumatic stress disorder: review to facilitate interpretation of VA/DOD Clinical Practice Guideline.
A well-documented association exists among Veterans' posttraumatic stress disorder (PTSD) symptoms, family relationship problems, and mental health problems in partners and children of Veterans. This article reviews the recommendations regarding couple/family therapy offered in the newest version of the Department of Veterans Affairs (VA)/Department of Defense (DOD) VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress. We then provide a heuristic for clinicians, researchers, and policy makers to consider when incorporating couple/family interventions into Veterans' mental health services. The range of research that has been conducted on couple/family therapy for Veterans with PTSD is reviewed using this heuristic, and suggestions for clinical practice are offered.


Working together: Heterotypic clusters and collective cell migration in melanoma metastasis.
In this issue of Developmental Cell, Campbell et al. (2021) show that melanoma cells with distinct invasive or proliferative gene signatures can form heterotypic clusters that extravasate collectively and readily seed the growth of metastatic lesions. These findings highlight interactions between heterogenous tumor cells as being critical for metastasis.


Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers.
Though early-stage colorectal cancer has a high 5 year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical and clinical investigations of immunotherapy for treatment of colorectal cancer including immune checkpoint blockade, adoptive cell therapy, monoclonal antibodies, oncolytic viruses, anti-cancer vaccines, and immune system modulators have been promising, but demonstrate limitations for patients with proficient mismatch repair enzymes. In this review, we discuss preclinical and clinical studies investigating immunotherapy for treatment of colorectal cancer and predictive biomarkers for response to these treatments. We also consider open questions including optimal combination treatments to maximize efficacy, minimize toxicity, and prevent acquired resistance and approaches to sensitize mismatch repair-proficient patients to immunotherapy.


Free thyroxine within the normal reference range predicts risk of atrial fibrillation.
Hyperthyroidism is a known precipitating factor for atrial fibrillation (AF). However, recent reports have suggested an increased risk of AF with free thyroxine (fT4) levels even within the upper reference (normal) range. We sought to test whether higher fT4 levels within the reference range are associated with an increased risk of AF. All patients in the Intermountain Healthcare electronic medical record database with an fT4 level not on thyroid medication were included. The reference range of fT4 was divided into quartiles (Q), and associations with prevalent and incident AF were assessed by multivariable regression. Similar analyses were performed for thyroid stimulating hormone (TSH) and total and free T3. A total of 174 914 patients were included and followed for 7.0 ± 4.9 years. Of these, 7.4%, 88.4%, and 4.2% had fT4 levels below, within, and above the reference range. As expected, prevalent AF was greater with elevated fT4. However, gradients also were noted within the reference range, comparing Q4 to Q1, for prevalent AF (adjusted odds ratio 1.4, P < .0001) and incident AF (adjusted hazard ratio 1.16, P < .0001). In contrast, no relationship with AF prevalence and incidence was noted for total and free T3 within their reference ranges, and the pattern for TSH was uninformative. Higher fT4 levels within the reference range were associated with an increased prevalence and incidence of AF. These findings in a large dataset prospectively validate earlier reports and may have important implications, including a redefinition of the normal range and fT4 targets for replacement therapy.


The effects of chronic administration of quetiapine on the methamphetamine-induced recognition memory impairment and dopaminergic terminal deficit in rats.
Previous studies have suggested that quetiapine, a new atypical antipsychotic drug, may have beneficial effects on cognitive impairment and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the therapeutic effects of chronic administration of quetiapine on methamphetamine (METH)-induced recognition memory impairment and dopaminergic terminal neurotoxicity in rats. Rats were pretreated with METH (5 mg/kg; s.c.) four times at 2-h intervals while their body temperature was monitored. Fifteen minutes after the last METH injection, rats were administered quetiapine (10 mg/kg/day; i.p.) for 28 days. One day after the last quetiapine injection, rats were trained and tested on an object recognition task on days 29 and 30. Finally, on day 31, rats were sacrificed for immunohistochemistry, 1 day after the object recognition task. METH induced hyperthermia, recognition memory impairment and a decrease of tyrosine hydroxylase immunoreactivity in the caudate putamen (CPu) of striatum. Quetiapine attenuated the METH-induced hyperthermia. Furthermore, chronic post-treatment of quetiapine reversed the METH-induced memory impairment and dopaminergic terminal deficit. These findings suggest that quetiapine may have therapeutic effects in the treatment of cognitive impairment and neurodegeneration induced by METH.


Repeat Evaluation of Lung Shunt Fraction is Unnecessary: A Retrospective Observational Study of Successive Lung Shunt Fractions from Variable Arterial Distributions in Patients Undergoing Radioembolization of Primary and Secondary Liver Tumors.
To evaluate whether the recalculation of lung shunt fraction (LSF) is necessary prior to next-stage or same lobe repeat radioembolization. Retrospective chart review was performed for patients who underwent radioembolization between February 2008 and December 2018. Eighty of 312 patients had repeat mapping angiograms and LSF calculations. A total of 160 LSF calculations were made using planar imaging (155, [97%]) and single-photon emission computed tomography (5 [3%]) technetium-99m macroaggregated albumin hepatic arterial injection imaging. The mean patient age was 61.8 years ± 12.7; 69 (86%) patients had metastatic disease and 11 (14%) had hepatocellular carcinoma. Patients had a median LSF of 5% (interquartile range [IQR] 3%-9%) with a median absolute difference of 1.25 (IQR 0.65-3.4) and a median of 76 days (IQR 42.5-120 days) between repeat LSF calculations. There was a median change in LSF of 0.2% between mapping studies (P = .11). There was no statistical significance between the repeat LSFs regardless of the arterial distribution (P = .79) or between tumor types (P = .75). No patients exceeded lung dose limits using actual or predicted prescribed dose amounts. The actual median lung dose was 2.6 Gy (IQR 1.8-4.4 Gy, maximum = 20.5) for the first radioembolization and 2.0 Gy (IQR 1.3-3.7 Gy, maximum = 10.1) for the second radioembolization. No significant difference in LSF was identified between different time points and arterial distributions within the same patient undergoing repeat radioembolization. In patients who receive well under 30-Gy lung dose for the initial treatment and a 50-Gy cumulative lung dose, repeat radioembolization treatments in the same patient may not require a repeat LSF calculation.


Fundus and histopathological study of radial optic neurotomy in the normal miniature pig eye.
To demonstrate the fundus and histopathological changes in the normal miniature pig eye after radial optic neurotomy. Ophthalmoscopic examinations, fundus photography, and fluorescein angiography were performed on 12 eyes that underwent radial optic neurotomy, 5 normal eyes, and 7 eyes that underwent vitrectomy (from 12 pigs in total) preoperatively and 1, 7, 14, 30, and 90 days postoperatively. These eyes were enucleated 120 days postoperatively. Sixteen eyes (of 8 pigs in total) that underwent radial optic neurotomy were enucleated 1, 3, 7, and 48 days (2 pigs each time) postoperatively. The enucleated eye sections were stained with hematoxylin-eosin, Masson trichrome, and Luxol fast blue. The retina radial to the site of radial optic neurotomy darkened gradually with the increasing curvature of the major retinal arteries. The filling time intervals from the retinal artery to the retinal vein were prolonged. At the incision site, there was a loss of nerve fibers, which were subsequently replaced by collagenous tissue. No anastomotic vessels formed by the end of the study. Postoperatively, the retinal circulation seemed somewhat sluggish compared with that seen preoperatively. Segmental retinal nerve atrophy eventually formed. The procedure itself may not be the sole factor for the formation of shunt vessels. To date, radial optic neurotomy is controversial and persuasive animal studies are lacking. In combining fluorescein angiography with histopathological examination, this study may be somewhat helpful.


Numb chin syndrome: an ominous clinical sign.
Numb chin syndrome (NCS) is a rare but important clinical symptom and sign. It describes a condition presenting as anaesthesia or paraesthesia over the chin, which is usually unilateral. The condition manifests spontaneously with no history of trauma, infection or obvious odontogenic cause. NCS is a clinically important finding as it may be the primary manifestation of Multiple Sclerosis (MS) or sign of systemic malignancy. We present a case of a 58-year-old gentleman who was referred to a regional oral and maxillofacial unit with a three-month history of sudden onset unilateral numbness of the chin. No odontogenic cause could be found and subsequent CT/PET scan from the cerebellum to the upper thighs revealed evidence of widespread metastatic disease. The patient died five weeks after his initial presentation. We discuss the importance of this clinical symptom, the likely mechanism of disease and offer differential diagnoses. Additionally, we recommend that patients presenting to their general dental practitioner with a numb chin be urgently investigated for a potentially undiagnosed malignancy or MS and be referred to their local oral and maxillofacial unit as an urgent 'target' referral.


Insights into the removal efficiencies of aged polycyclic aromatic hydrocarbons in humic acids of different soil aggregate fractions by various oxidants.
Chemically oxidative removal of polycyclic aromatic hydrocarbons (PAHs) in soil is related to their occurrence state. Whether the heterogeneity of natural organic matter has an effect on the occurrence of PAHs in soil and, if there is an effect, on the oxidative removal efficiency of PAHs remains unknown. In this study, the removal efficiencies of 16 priority PAHs aged in humic acids (HAs) of different soil aggregate fractions by various oxidants were investigated by combining soil fractionation and microreaction experiments. Results showed that the accumulations of PAHs in particulate HA (P-HA) and microaggregate occluded HA (MO-HA) mainly occurred in the early period of the aging time frame. In contrast, PAH accumulation in non-aggregated silt and clay associated HA (NASCA-HA) was relatively slow and tended to saturate in the late period of the aging time frame. The cumulative contents of PAHs throughout the entire aging period in MO-HA and NASCA-HA were significantly greater than that in P-HA. The aged PAHs in P-HA and NASCA-HA exhibited the highest and lowest removal efficiencies, respectively. This ranking was mainly governed by the molecular size and polarity of HAs. Sodium persulfate and potassium permanganate had the highest removal efficiencies in total PAHs in HAs, with average efficiencies of 85.8% and 79.1%, respectively, in P-HA. Hydrogen peroxide had the lowest degradation efficiency in PAHs. In particular, the degradation efficiency of total PAHs in NASCA-HA was lowered to 31.0%. PAH congeners in HAs showed a large difference in oxidative removal efficiency. Low-ring PAH was more easily degraded than medium- and high-ring PAHs, and in most treatments, fluoranthene and pyrene in the medium ring and benzo[a]pyrene in the high ring demonstrated higher efficiencies than other PAHs with the same number of rings. Our findings are useful in promoting the accurate and green remediation of PAH-contaminated soils.


Occupancy model of perceived numerosity.
Observers saw 234 different pairs of stochastically organized dot patterns and indicated which of the two patterns appeared to be more numerous. All of the data can be accounted for by supposing that the choice of the more numerous pattern is based on the determination of the occupancy indices of both patterns. Each dot is posited to have an impact upon its neighborhood in a constant occupancy radius R. The area of the stimulus plane occupied collectively by all dots provides a basis for judging relative numerosity; the pattern with the larger occupancy value is chosen as more numerous. The occupancy model, besides providing a general explanation of known numerosity illusions in strictly quantitative terms, can explain some puzzling aspects of numerosity perception.


The uptake and distribution of [3H]benzo[a]pyrene in the Northern pike (Esox lucius). Examination by whole-body autoradiography and scintillation counting.
The uptake and distribution of the polyaromatic hydrocarbon benzo[a]pyrene in Northern pike (Esox lucius) were investigated by whole body autoradiography and scintillation counting. [3H]Benzo[a]pyrene was administered either in the diet or in the water. The levels of this xenobiotic employed corresponded to levels found in moderately polluted water. The uptake and distribution of this compound and its metabolites were followed from 10 hr to 21 days after the initial exposure. The autoradiography patterns observed here with both routes of administration suggest, as expected, that benzo[a]pyrene is taken up through the gastrointestinal system and the gills, metabolized in the liver, and excreted in the urine and bile. Other findings indicate that the gills may not be a major route of excretion for benzo[a]pyrene and its metabolites in the Northern pike; that benzo[a]pyrene may be taken up from the water directly into the skin of this fish; that benzo[a]pyrene and its metabolites are heterogeneously distributed in the kidney of the Northern pike; and that very little radioactivity accumulates in the adipose tissue. With scintillation counting, uptake of radioactivity from the water was found to occur rapidly in all organs, reaching a plateau in most cases after about 0.8 days. The concentrations of radioactivity in different organs ranged between 50 (many organs) and 80,000 (gallbladder + bile) times that found in the surrounding water. Since most of the radioactivity recovered in different organs of the pike after 8.5 days of exposure was in the form of metabolites, we feel that metabolism may play an important role in the bioconcentration of xenobiotics in fish.


Implant-Mediated Guided Growth for Coronal Plane Angular Deformity in the Pediatric Patient with Patellofemoral Instability.
Pediatric patellofemoral instability is a complex problem, for which there are several anatomic risk factors. Coronal plane malalignment (i.e., genu valgum) is one cause of patellofemoral instability, and treatment of genu valgum has been associated with improved patellofemoral stability. Coronal plane angular deformity correction, typically achieved by distal femoral osteotomy in the adult population, can be achieved with less invasive surgical techniques in pediatric patients using implant-mediated guided growth. By temporarily tethering one side of an open physis to generate differential growth in the coronal plane, valgus malalignment can be corrected. We present our technique for medial distal femoral implant-mediated guided growth using tension band plating for treatment of pediatric patellofemoral instability associated with genu valgum. This technique is minimally invasive, has a low complication rate, and in conjunction with conventional treatment can reduce the risk of recurrent instability.


Prosthesis extrusion post total ossicular replacement ossiculoplasty (TORP) following isotretinoin use: A case report and literature review of peri-operative isotretinoin safety.
Ossiculplasty is the preferred intervention to restore the mechanism of sound transmission in patients with ossicular deformities. Here, we present a case of a young female who underwent cartilage tympanoplasty with total ossicular replacement prosthesis (TORP) to the right ear. Her recovery was progressing well with signs of postoperative improvements for almost two years until she was started on Isotretinoin 40 mg by her dermatologist. A few months later, she presented with worsening hearing loss and bloody discharge to the same ear. Consequently, examination showed that part of the prosthetic device was extruding through the cartilage graft, with signs of graft thinning and documented conductive hearing loss. Although it is evident that isotretinoin has an impact on various healing processes. Literature varies on the recommendations on the use of isotretinoin before and after surgical procedures and the exact magnitude of impact is still to be determined. Our case suggests that using oral Isotretinoin may lead to the thinning of cartilage graft and thus extruding of the prosthesis. Clinicians must be aware of the possible adverse associations of oral Isotretinoin to healing, especially surgeries involving extremely delicate skin or cartilage grafts like in our case.


Psychometric Properties of a Revised Form of the Drug-Taking Confidence Questionnaire for Use with Adolescents.
Self-efficacy is an important cognitive predictor of substance abuse treatment outcome. While measures of coping self-efficacy are related to substance use relapse in adults, their properties are not well known in adolescent populations. The present study examined 223 adolescents while in treatment for substance abuse and comorbid psychiatric disorders. Responses on the Drug-Taking Confidence Questionnaire (DTCQ; Sklar et al., 1997) were used to construct a 37-item, 5-factor version for use with adolescents. Exploratory and confirmatory factor analysis identified the following factors: 1) Negative Situations, 2) Social/Drugs, 3) Pleasant Emotions, 4) Testing Personal Control, and 5) Physical/Intimate. Data preliminarily support the construct, concurrent, and predictive validity of the revised instrument.


Haemodynamic effects of changes in atrioventricular and interventricular delay in cardiac resynchronisation therapy show a consistent pattern: analysis of shape, magnitude and relative importance of atrioventricular and interventricular delay.
To assess the haemodynamic effect of simultaneously adjusting atrioventricular (AV) and interventricular (VV) delays. 35 different combinations of AV and VV delay were tested by using digital photoplethysmography (Finometer) with repeated alternations to measure relative change in systolic blood pressure (SBP(rel)) in 15 patients with cardiac resynchronisation devices for heart failure. Changing AV delay had a larger effect than changing VV delay (range of SBP(rel) 21 v 4.2 mm Hg, p < 0.001). Each had a curvilinear effect. The curve of response to AV delay fitted extremely closely to a parabola (average R2 = 0.99, average residual variance 0.8 mm Hg2). The response to VV delay was significantly less curved (quadratic coefficient 67 v 1194 mm Hg/s2, p = 0.003) and therefore, although the residual variance was equally small (0.8 mm Hg2), the R2 value was 0.7. Reproducibility at two months was good, with the SD of the difference between two measurements of SBP(rel) being 2.5 mm Hg for AV delay (2% of mean systolic blood pressure) and 1.5 mm Hg for VV delay (1% of mean systolic blood pressure). Changing AV and VV delays results in a curvilinear acute blood pressure response. This shape fits very closely to a parabola, which may be valuable information in developing a streamlined clinical protocol. VV delay adjustment provides an additional, albeit smaller, haemodynamic benefit to AV optimisation.


Trends in the Intraindividual Double Burden of Overweight/Obesity and Anemia among Adult Women Living in 33 Low- and Middle-Income Countries: A Secondary Analysis of Demographic and Health Surveys from 2000-2019.
Changes in overweight/obesity and anemia among women have been investigated in multiple studies, but the rate at which their coexistence at the individual level has evolved remains unknown. We aimed to 1) document trends in the magnitude and inequalities of the co-occurrence of overweight/obesity and anemia; and 2) compare these with overall trends in overweight/obesity, anemia, and the co-occurrence of anemia with normal weight or underweight. For this cross-sectional series study, we used 96 Demographic and Health Surveys from 33 countries with available anthropometric and anemia data among nonpregnant adult women (20-49 y old; n = 1,648,308). The primary outcome was defined as the coexistence of overweight or obesity (BMI ≥25kg/m2) and anemia (hemoglobin concentrations <12.0 g/dL) within the same individual. We computed overall and regional trends through multilevel linear regression models and by sociodemographic characteristics (i.e., wealth, education, and residence). Estimates at the country level were calculated through ordinary least square regression models. From 2000 to 2019, the co-occurrence of overweight/obesity and anemia increased modestly at an annual rate of 0.18 percentage points (95% CI: 0.08, 0.28 percentage points; P < 0.001), ranging from 0.73 percentage points in Jordan to -0.56 percentage points in Peru. This trend occurred in parallel with overall increases in overweight/obesity and reductions in anemia. The co-occurrence of anemia with normal weight or underweight was reducing in all countries, except Burundi, Sierra Leone, Jordan, Bolivia, and Timor-Leste. Stratified analyses yielded an upward trend in the co-occurrence of overweight/obesity and anemia across all subgroups but particularly in women from the 3 middle wealth groups, no education, and capital city or rural residents. The rising trend in the intraindividual double burden suggests that efforts to reduce anemia among women living with overweight/obesity may need to be revisited to accelerate progress toward the 2025 global nutrition target of halving anemia.


Usefulness of inspiratory capacity measurement in COPD patients in the primary care setting.
To determine if inspiratory capacity (IC) assessment could be useful for chronic obstructive pulmonary disease (COPD) patient management in the primary care setting. A descriptive cross-sectional study was conducted in 93 patients diagnosed with COPD according to Spanish Thoracic Society (SEPAR) criteria. Patients were recruited in eight primary care centers in Andalusia, Spain. Anthropometric, sociodemographic, resting lung function (forced expiratory volume in one second [FEV(1)], forced vital capacity, synchronized vital capacity, IC), and quality of life data based on the Spanish version of Saint George's Respiratory Questionnaire (SGRQ) were obtained. LUNG FUNCTION RESULTS EXPRESSED AS PERCENTAGES OF THE PREDICTED VALUES WERE AS FOLLOWS: FEV(1), 49.04 (standard deviation [SD]: 16.23); IC, 61.73 (SD: 15.42). The SGRQ mean total score was 47.5 (SD 17.98). The Spearman's Rho correlation between FEV(1) and SGRQ was r = -0.36 (95% confidence interval [CI]: -0.529 to -0.166), between IC and SGRQ was r = -0.329 (95% CI -0.502 to -0.131), and between FEV(1) and IC was r = -0.561. Measurement of IC at rest could be used as a complementary functional exploration to forced spirometry in the monitorization of patients with COPD in the primary care setting. We found a poor correlation between IC and quality of life at the same level as in FEV(1).


A transnasal intracranial stab wound by a plastic-covered umbrella tip.
A 48-year-old man died from a transnasal intracranial stab wound caused by an umbrella. The track of the stab passed from the right nostril, through the sphenoid sinus, the left side of the sella turcica and anterior clinoid process, and finally reached the surface of the brain. The stab wound crossed the left internal carotid artery, causing an exsanguination and aspiration of blood into the airway, resulting in death. It is extremely rare that an umbrella tip used during a struggle would stab the nostril of the victim. Transnasal intracranial stab wounds can be overlooked and require sensitive handling.


The Calcium Carbonate Breath Test, a noninvasive test of stimulated gastric acid secretion: preliminary communication.
Gastric acid secretion is subject to complex control mechanisms, and varies widely between individuals and populations. Its measurement has previously required intubation of the stomach with ingestion of a test meal or injection of a secretion stimulant. We describe a novel method of measuring gastric acid secretion noninvasively - the Calcium Carbonate Breath Test. 13C-labelled calcium carbonate is ingested by a fasting participant. The carbonate neutralizes gastric acid to produce 13CO2, which is expired in the breath. Measurement of the excess 13CO2 in the breath allows back-calculation of the amount of gastric acid secreted during the test, provided that other variables affecting CO2 production and excretion are minimized or controlled for. Studies on a single healthy individual have shown reproducible estimations of acid secretion and over 80% suppression of acid secretion after the proton pump inhibitor treatment. The method seems to be promising, but further studies on other individuals need to be carried out. The Calcium Carbonate Breath Test may have wide applications in epidemiological studies, clinical management of acid-related diseases, screening for hypochlorhydria and development of new acid-suppressing treatments.


The comparison of solid phase and fibrin plate methods for the measurement of plasminogen activators.
A rapid and highly sensitive solid phase assay was compared with the fibrin plate method for the measurement of urokinase, streptokinase and the plasminogen activators in human euglobulin fractions. The solid phase assay was run using glu - or lys - plasminogen, and significant differences were observed in the activation of the plasminogens by urokinase and streptokinase. Plasminogen activator levels in euglobulin fractions were also measureable. Very good agreement was obtained between the fibrin plate and solid phase methods in all cases.


Heerfordt syndrome: a cause of facial paralysis.
Heerfordt syndrome is an unusual manifestation of systemic sarcoidosis and is characterized by parotitis, uveitis, and facial nerve paralysis. A case is presented and the clinical manifestations are discussed. Angiotensin converting enzyme assays along with tissue biopsy demonstrating noncaseating granulomas confirm the diagnosis.


Automated assays for superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity.
Automated assays for catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase are presented. The assay for catalase is based on the peroxidatic activity of the enzyme. The glutathione peroxidase and reductase assays measure the consumption of NADPH following the reduction of t-butyl hydroperoxide and oxidized glutathione, respectively. The assay for superoxide dismutase is based on the reduction of cytochrome c. All assays utilize the Cobas FARA clinical automated analyzer and provide considerable time savings over the manual assays.


Protein-based fluorescent metal nanoclusters for small molecular drug screening.
A facile drug screening method based on synthesis of fluorescent gold nanoclusters inside albumin proteins loaded with small molecular drugs and comparing the relative fluorescence intensities of the resultant gold nanoclusters has been developed and successfully applied for the quantitative measurement of drug-protein binding constants.


Sensitivity and specificity of increased pulse pressure as a diagnostic test for K/DOQI stage III-b CKD.
Increased pulse pressure (IPP) is associated with an estimated glomerular filtration ≤ 60/mL/min/1.73 m2; thus, it can be useful as a diagnostic test to identify people with K/DOQI stage III-b chronic kidney disease (CKD). To determine the usefulness of IPP as a diagnostic test for K/DOQI stage III-b CKD. Diagnostic test study that included adult patients without comorbidities, registered in the Health Workers Cohort. The CKD-EPI formula was used to calculate glomerular filtration. Pulse pressure was determined by subtracting diastolic from systolic blood pressure. Sensitivity, specificity, positive predictive value, negative predictive value and prevalence were calculated using standard formulas. A ROC curve was generated to determine the area under the curve. A total of 6,215 patients were included. An IPP ≥ 50 mmHg was observed to have a sensitivity of 74 %, specificity of 70 %, positive predictive value of 1 %, negative predictive value of 100 % and a prevalence of 1 %. The inflection point in the ROC curve to identify K/DOQI III-b CKD was 0.71. An IPP ≥ 50 mmHg is useful as a diagnostic test to identify people with K/DOQI stage III-b CKD.


Sensory neuron growth cones comigrate with posterior lateral line primordial cells in zebrafish.
The development of neuromasts and sensory neurons of the posterior lateral line was studied in zebrafish (Brachydanio rerio) in order to determine the relationship between growing axons of sensory neurons and the migratory cellular primordium of midbody line neuromasts. Scanning electron microscopy revealed that a primary system of six neuromasts develops during the second day after fertilization and evidence is presented that these arise from cells of a migratory primordium. The primordium is first detected in the postauditory region immediately adjacent to the developing sensory ganglion. Growth cones of posterior lateral line sensory neurons are found within the premigratory primordium when it is adjacent to the ganglion. At later times growth cones of these sensory neurons are found within the primordium as it migrates caudally along the midbody line. These results demonstrate that although the growth cones of the sensory neurons grow over a considerable distance to their final destination, they are never very far from their target cells (or target cell precursors), which migrate with them and may even lead them.


State-of-the-art machine learning algorithms for the prediction of outcomes after contemporary heart transplantation: Results from the UNOS database.
We sought to develop and validate machine learning (ML) models to increase the predictive accuracy of mortality after heart transplantation (HT). We included adult HT recipients from the United Network for Organ Sharing (UNOS) database between 2010 and 2018 using solely pre-transplant variables. The study cohort comprised 18 625 patients (53 ± 13 years, 73% males) and was randomly split into a derivation and a validation cohort with a 3:1 ratio. At 1-year after HT, there were 2334 (12.5%) deaths. Out of a total of 134 pre-transplant variables, 39 were selected as highly predictive of 1-year mortality via feature selection algorithm and were used to train five ML models. AUC for the prediction of 1-year survival was .689, .642, .649, .637, .526 for the Adaboost, Logistic Regression, Decision Tree, Support Vector Machine, and K-nearest neighbor models, respectively, whereas the Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score had an AUC of .569. Local interpretable model-agnostic explanations (LIME) analysis was used in the best performing model to identify the relative impact of key predictors. ML models for 3- and 5-year survival as well as acute rejection were also developed in a secondary analysis and yielded AUCs of .629, .609, and .610 using 27, 31, and 91 selected variables respectively. Machine learning models showed good predictive accuracy of outcomes after heart transplantation.


Fold-change Response of Photosynthesis to Step Increases of Light Level.
Plants experience light intensity over several orders of magnitude. High light is stressful, and plants have several protective feedback mechanisms against this stress. Here we asked how plants respond to sudden rises at low ambient light, far below stressful levels. For this, we studied the fluorescence of excited chlorophyll a of photosystem II in Arabidopsis thaliana plants in response to step increases in light level at different background illuminations. We found a response at low-medium light with characteristics of a sensory system: fold-change detection (FCD), Weber law, and exact adaptation, in which the response depends only on relative, and not absolute, light changes. We tested various FCD circuits and provide evidence for an incoherent feedforward mechanism upstream of known stress response feedback loops. These findings suggest that plant photosynthesis may have a sensory modality for low light background that responds early to small light increases, to prepare for damaging high light levels.


Common precursor of lysozymes of hen egg-white and bacteriophage T4.
The lysozymes of hen egg-white and bacteriophage T4 have similar catalytic properties but their amino acid sequences are not homologous. The question therefore arises whether they are derived from a common ancestral protein or have arisen independently. On the basis of the data we have gathered, it is shown here that the two enzymes are similar in the conformation of their backbones, in their modes of binding substrates, in specific protein--substrate interactions and in their presumed modes of action. We conclude that the two enzymes have diverged from a common precursor. This seems to be the most convincing example to date of the divergence of proteins with nonhomologous amino acid sequences.


Clinical Use of Impedance Cardiography for Hemodynamic Assessment of Early Cardiovascular Disease and Management of Hypertension.
This article is for clinicians considering impedance cardiography (ICG) for secondary prevention. ICG is an inexpensive noninvasive technology that can be used to assess hemodynamic function of the central cardiovascular system. Diverse abnormalities of ventricular function, systolic and diastolic, can be detected by ICG. Additional data pertaining to decompensation can be obtained by taking ICG readings with the patient performing postural change, from upright to supine, to quantify the compensatory response. Vascular load consists of resistive and pulsatile loads. Systemic vascular resistance can provide a measure of resistive load. Pulsatile load has two components: arterial stiffness and wave reflection. ICG can be used to calculate arterial compliance and detect aortic wave reflection. For stage 1 hypertension, a significant issue is whether a treating clinician should add pharmacotherapy to lifestyle modification. Adults who have multiple cardiovascular risk factors with stage 1 hypertension have early cardiovascular disease. ICG can be used to identify the functional abnormalities associated with the cardiovascular disease. For the management of hypertension, ICG can be used to calculate the underlying hemodynamic parameters of cardiac index and systemic vascular resistance associated with a patient's blood pressure. There can be wide ranges for cardiac index and systemic vascular resistance, with many patients having low cardiac index with high systemic vascular resistance or vice versa. These hemodynamic data can be used to customize pharmacotherapy. Drug titration can be guided by patient response to treatment using the initial hemodynamic data as a baseline for comparison to subsequent measurements from serial office visits.


Confocal Microscopy Confirmed that in Phosphatidylcholine Giant Unilamellar Vesicles with very High Cholesterol Content Pure Cholesterol Bilayer Domains Form.
The cholesterol (Chol) content in the fiber cell plasma membranes of the eye lens is extremely high, exceeding the solubility threshold in the lenses of old humans. This high Chol content forms pure Chol bilayer domains (CBDs) and Chol crystals in model membranes and membranes formed from the total lipid extracts from human lenses. CBDs have been detected using electron paramagnetic resonance (EPR) spin-labeling approaches. Here, we confirm the presence of CBDs in giant unilamellar vesicles prepared using the electroformation method from Chol/1-palmitoyl-2-oleoylphosphocholine and Chol/distearoylphosphatidylcholine mixtures. Confocal microscopy experiments using phospholipid (PL) analog (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-5,5'-disulfonic acid) and cholesterol analog fluorescent probes (23-(dipyrrometheneboron difluoride)-24-norcholesterol) were performed, allowing us to make three major conclusions: (1) In all membranes with a Chol/PL mixing ratio (expressed as a molar ratio) >2, pure CBDs were formed within the bulk PL bilayer saturated with Chol. (2) CBDs were present as the pure Chol bilayer and not as separate patches of Chol monolayers in each leaflet of the PL bilayer. (3) CBDs, presented as single large domains, were always located at the top of giant unilamellar vesicles, independent of the change in sample orientation (right-side-up/upside-down). Results obtained with confocal microscopy and fluorescent Chol and PL analogs, combined with those obtained using EPR and spin-labeled Chol and PL analogs, contribute to the understanding of the organization of lipids in the fiber cell plasma membranes of the human eye lens.


Optimum investments in project evaluations: when are cost-effectiveness analyses cost-effective?
This manuscript extends the classical models of the value of information to ask whether a hospital's net financial return is ever maximized by a cost-effectiveness analysis of retrospective data when watchful waiting and a full randomized clinical trial are alternative methodologies. The manuscript demonstrates that (1) some small-scale retrospective analyses may negatively affect net income and (2) under some conditions, larger-scale retrospective analyses may maximize net income. The manuscript also suggests that risk aversion increases the value of information and therefore the optimum expenditure on a project evaluation.


Hypomelanosis of Ito. Report of a case and review of the literature.
A 5-month-old boy with hypomelanosis of Ito was studied. Lesions presented as bizarre, hypopigmented whorls and streaks. Histologic studies showed that the hypopigmented areas contained normal melanocytes with decreased content of intracellular melanin. A review of the literature revealed the disease to be a discrete entity of hypopigmentation associated with a high percentage of central nervous system abnormalities, particularly seizure disorders and mental retardation.


Nucleário, cardboard, or manual crowning: which maintenance technique is most cost-effective in tree seedling survival establishment?
In ecological restoration, one of the main challenges is to develop new methods, techniques, and incentives that both favour and reduce maintenance costs in restoration projects. Besides, post-planting maintenance is often neglected hampering seedling survival over time owing to alien grasses, which compete strongly with native plants for resources. To solve these issues, recently, an innovative technology called Nucleário has been developed in Brazil. Aiming to hinder alien competition filters, the Nucleário also attempts to condition a better microenvironment, reducing drought stress through the water storage tank, decreasing temperatures, which facilitates the survival and growth of seedlings in areas under restoration. Another method used to decrease alien grasses, which is inexpensive, is seedling crowning using cardboard lowing maintenance needs in restored areas. Cardboard has similar functions to Nucleário, such as protecting soil against loss of water and nutrients and reducing competition with invasive exotic grasses. Therefore, comparing them also with traditional manual weeding (i.e., clean-weeded crown by hoe), we aimed to verify which technique is most cost-efficient for seedling crown maintenance of Dipteryx alata Vog., which is an indigenous tree species with high economic value owing to its nuts. We tested three techniques in areas under restoration in the Cerrado, in the Environmental Protection Area "Córrego Guariroba" located in Campo Grande, Mato Grosso do Sul, Brazil. We monitored seedlings submitted to the three methods in the wet and the dry periods for biotic (competition with exotic grasses, herbivory, and growth) and abiotic (moisture and soil temperature) indicators. We observed that the Nucleário was the treatment that maintained the highest soil moisture, resulting in a larger canopy area. However, these effects do not reflect increases in the survival rate, diameter, and height of the seedlings. None of the treatments was effective in reducing herbivory. Nucleário was the most effective treatment in reducing the competition of seedlings with invasive grasses. Cardboard presented an implementation value 21.5 times lower than Nucleário and 1.2 times than manual crowning. Given the high purchase price, the Nucleário's cost-benefit ratio was very high compared to the crowning of cardboard and the manual weeding, which discourages us from recommending it for this species with high survival rates. Its project can be revised to decrease herbivory rates, as well as its efficiency tested in the short and long term in different ecosystems and species, particularly species susceptible to water stress.


The electrical conductance of semipermeable membranes. I. A formal analysis.
A kinetic analysis of membrane conductance under conditions of stationary flow is presented. The semipermeable membrane is idealized as a homogeneous laminar phase separating ionic solutions on either side. It is assumed, without consideration of the mechanisms involved, that some ion species permeate the membrane while others do not. The flux of a given species is taken to be linearly related to the gradient of its concentration and to the electric field. The resulting flow equations, when combined with Poisson's equation, permit the formulation of the conductance problem in terms of a set of non-linear differential equations. They describe the spatial variation of the electric displacement and contain the ion current densities as parameters. Their integration, subject to appropriate boundary conditions, fixes the values of these parameters and of the corresponding transmembrane potential. The solution of the conductance problem cannot, however, be carried through in analytic form. The numerical analysis of a number of special cases will be presented in subsequent publications.


Bivalent biogenic amine reuptake inhibitors.
A series of aryltropane-based bivalent ligands was prepared and investigated for binding potency and for their ability to inhibit reuptake of human dopamine, serotonin and norepinephrine transporters. The bivalent ligand 4, comprised of linking an aryltropane by an octamethylene spacer showed high efficacy for the human dopamine transporter and had a discrimination ratio of 130.


Adrenergic innervation of blood vessels. A fluorescence microscopic study of the eighth nerve and inner ear structures in man.
Fluorescence microscopy was used to examine the perivascular adrenergic innervation in the eighth nerve and vestibular end-organ specimens from 13 patients with otoneurological diseases. It was observed that all the blood vessels accompanying the cochlear and vestibular nerves from patients with acoustic neuroma or Meniere's disease were devoid of specifically fluorescent fibers, while several adrenergic fibers were seen around the arterioles accompanying the inferior vestibular nerve from the patient with sudden deafness.


Unusual Malignant Thoracic Cystic Lesion.
Malignant cystic lesions in the spine are rare. In this report, we present a 65-year-old man who presented with imbalance on walking of 1-week duration with intact motor examination. Magnetic resonance imaging of the thoracic spine showed large expansile, T2-hyperintense mass involving T8 vertebral body, replacing the posterior elements causing cord compression with associated edema. He underwent uneventful T8 corpectomy, placement of expandable interbody cage, and T5-T11 posterolateral fusion using bilateral transpedicular approach. However, he died 5 months later due to progression of moderately differentiated metastatic lung cancer. To our knowledge, this is the first report showing the near-complete replacement of vertebral body and posterior elements with a malignant cystic lesion.


[Genetic variability and the origin of house mouse from the territory of Russia and neighboring countries].
Genetic differentiation and gene geographic variation of house mouse from the territory of Russia and neighboring countries was examined based on the allozyme analysis of samples from natural, semisynanthropic, and obligate synanthropic populations. The results of analysis of genetic differentiation, performed using 22 interpreted loci, as well as the data on gene geographic variation of four allozyme markers (Idh-1, Sod-1, Aat-1, and hemoglobin) validated the hypothesis on rapid mice expansion from the south of Eastern Europe to the Pacific coast of Asia. It was demonstrated that moving eastwards led to the formation currently expanding zones of hybridization between the "northern" M. musculus group and the "Central Asian" M. wagneri group in Siberia, and with the M. castaneus group in the south of the Russian Far East. The allozyme data were compared with the data of molecular genetic and karyological analyses performed using the same experimental material. The phenomenon of hybrid zones of the house mouse from Eurasia is discussed.


Recommendations for a change in living situation resulting from an outpatient geriatric assessment: type, frequency and risk factors.
We analyzed the outcomes of 480 comprehensive outpatient geriatric assessments to determine the frequency of recommendations for home help or a change in residence and to determine whether simple clinical observations could predict such recommendations. Fifty-eight percent (280) of the patients received no recommendation for a change in the living situation. Of the 200 patients receiving a recommendation for a change in living situation, 97 (49%) were felt to be able to stay at home with increased in-home support and/or day care, and 51.5% (103) were advised to seek placement. After adjusting for age and gender, risk factors predicting a recommendation for change were dementia (odds-ratio = 9.98), vision deficits (odds ratio = 2.02), lower education level compared to college (odds-ratio = 1.88 high school, 1.42 for less than high school), an increasing number of medical diagnoses (odds-ratio = 1.49 per diagnosis), and a functional impairment on the Katz index (odds-ratio = 1.09). The presence of these risk factors should lead to consideration of further evaluation of the home environment in this study. We conclude that geriatric patients presenting for a comprehensive outpatient evaluation commonly need a change in home situation, though most can remain in their home, and that simple clinical observations can be helpful in screening patients for further evaluation of their home environment.


Timing of developmental reduction in epithelial glutathione redox potential is associated with increased epithelial proliferation in the immature murine intestine.
BackgroundThe intracellular redox potential of the glutathione (GSH)/glutathione disulfide (GSSG) couple regulates cellular processes. In vitro studies indicate that a reduced GSH/GSSG redox potential favors proliferation, whereas a more oxidized redox potential favors differentiation. Intestinal growth depends upon an appropriate balance between the two. However, how the ontogeny of intestinal epithelial cellular (IEC) GSH/GSSG redox regulates these processes in the developing intestine has not been fully characterized in vivo.MethodsOntogeny of intestinal GSH redox potential and growth were measured in neonatal mice.ResultsWe show that IEC GSH/GSSG redox potential becomes increasingly reduced (primarily driven by increased GSH concentration) over the first 3 weeks of life. Increased intracellular GSH has been shown to drive proliferation through increased poly-ADP-ribose polymerase (PARP) activity. We show that increasing IEC poly-ADP-ribose chains can be measured over the first 3 weeks of life, indicating an increase in IEC PARP activity. These changes are accompanied by increased intestinal growth and IEC proliferation as assessed by villus height/crypt depth, intestinal length, and Ki67 staining.ConclusionUnderstanding how IEC GSH/GSSG redox potential is developmentally regulated may provide insight into how premature human intestinal redox states can be manipulated to optimize intestinal growth and adaptation.


Dietary acrylamide does not increase colon aberrant crypt foci formation in male F344 rats.
Acrylamide, a known rodent and a probable human carcinogen, is spontaneously formed in foods cooked at high temperature. We studied the role of dietary acrylamide in modulating the early stages of colon carcinogenesis and assessed if dietary fat level was critical in altering the effects of acrylamide. Male F344 rats were subcutaneously injected with azoxymethane and were simultaneously randomized into 8 dietary groups (n=8 rats/group). Diets were based on AIN-93G semi-synthetic formula modified to contain either low fat (7% corn oil) or high fat (23.9% corn oil) and acrylamide at 0, 5, 10 or 50 mg/kg diet (wt/wt). All rats received the experimental diets ad libitum for 8 weeks, after which they were killed and their colons assessed for aberrant crypt foci (ACF), putative precancerous lesions. Irrespective of dietary fat level, rats with the highest tested dose of acrylamide (50 mg/kg diet) had significantly lower total ACF (p<0.05) and lower large ACF (those with 4 or more crypts/focus; p<0.001) compared with their respective controls (0 mg/kg diet). A significantly lower number of large ACF (p=0.046) was noted in rats treated with 10 mg/kg diet acrylamide exclusively in the high fat group, compared to the high fat control. This short-term bio-assay to test carcinogenicity of dietary acrylamide in the colon demonstrates that acrylamide, when administered through the diet at doses known to cause rat tumors, does not increase the risk of developing azoxymethane-induced precancerous lesions of the colon in rats. On the contrary, a high dose of dietary acrylamide decreased the growth of precancerous lesions in both low and high fat diet regimens in this model.


Calcium metabolism in intact isolated thymocytes.
Isolated rat thymocytes incubated under proper metabolic conditions extrude Ca2+ previously taken up under metabolically unfavourable conditions. The extrusion can be supported by both respiratory and glycolytic energy but glycolysis seems to be more efficient for this purpose. La3+ (50--200 micron) and the ionophore A 23187 inhibit cell Ca2+ extrusion. Ruthenium Red (1--100 micron) does not influence cell Ca2+ extrusion while it inhibits the in situ mitochondrial cation uptake. All the results are consistent with a cell regulation model of Ca2+ content in which both plasma membrane and mitochondria co-operate, acting in opposite directions, in order to decrease cytosolic Ca2+ concentration. The possibility of Na+-Ca2+ hetero-exchange participation to cell Ca2+ homeostasis regulation is also discussed.


Social-cognitive correlates of CPAP adherence in experienced users.
Obstructive sleep apnea (OSA) is a condition with serious medical and psychosocial consequences. However, poor adherence with nasal continuous positive airway pressure (CPAP) treatment limits the effectiveness of treatment. Behavior change factors offer one avenue of research to better understand the correlates of CPAP adherence. Fifty-eight participants who had been diagnosed with OSA and prescribed CPAP treatment agreed to complete questionnaires that assessed sleep apnea symptoms, behavior change factors, and CPAP side effects, and to have their CPAP data downloaded. Behavior change factors from both social cognitive theory (SCT) and the transtheoretical model (TM) were assessed. The primary aim of the study was to examine the relationship between these social-cognitive factors and objectively measured CPAP adherence. Participants had been using CPAP for a mean of 2.1 years. SCT variables (adjusted R(2)=0.115, P=.008) and TM variables (adjusted R(2)=0.157, P<.0001) each accounted for a statistically significant amount of variance in CPAP adherence. The results suggest that social-cognitive factors may be associated with CPAP adherence in experienced CPAP users. The principal advantage to these theory-driven and empirically validated factors is that they are modifiable and can provide the basis for effective interventions to increase CPAP adherence.


Healthcare Utilization Patterns Among Children With a History of Child Protective Services Investigations.
Examine whether children with a prior child protective services (CPS) investigation had different healthcare utilization compared to children without a history of CPS investigations. The Children's Health Assessment and Planning Survey assessed 6,492 primary caregivers of children ages 0-17 years residing in North Texas in 2015. Caregivers reported prior CPS investigations and child healthcare utilization (emergency department [ED] use, unmet medication needs, and unmet medical care needs). A total of 408 (5%) caregivers reported their child had a CPS investigation. Children with CPS investigations had greater odds of visiting the ED (OR = 1.9; 95% CI: 1.4, 2.5) and not receiving necessary medical care (OR = 1.9; 95% CI: 1.4, 2.8) compared to children without a CPS investigation. Prior CPS investigation was associated with disparities in receipt of necessary medical care and ED utilization for children.


Combining Participatory Mapping and Geospatial Analysis Techniques to Assess Wildfire Risk in Rural North Vietnam.
Participatory mapping (PM) is a valuable research tool for assessing fire risk, especially in regions where data are difficult to collect or inconsistent; in such areas, the integration between crowdsourced data and geospatial techniques plays a fundamental role in gathering more consistent and reliable information. This study combines a participatory (community-based) mapping approach with geospatial techniques to assess fire risk in Van Chan district, northern Vietnam, an area where the economy relies mainly on forestry activities. Local stakeholders designed a map of wildfires, which was modelled as a function of a set of physical and socio-economic variables. A fire-probability map of the district was obtained and compared with MODIS data (2000-2020). The results suggest that higher fire probability occurs in areas with lower human pressure, and they provide information on related socio-economic drivers that affect this phenomenon. This study highlights the importance of combining participatory approaches and geospatial techniques to assess fire dynamics and prevent wildfires in terms of understanding and predicting the risks. The involvement of local communities is fundamental to this innovative participatory approach with regard to better supporting decision-making and prevention actions and to developing fire control management guidelines.


The entomopathogenic fungus Metarhizium anisopliae enhances Arabidopsis, tomato, and maize plant growth.
Species of the entomopathogenic fungi Metarhizium are used worldwide as biocontrol agents. Recently, other lifestyles have been associated with some Metarhizium species, which include their role as saprophytes, endophytes, and plant growth promoters. Herein, the effect of three Metarhizium anisopliae strains on the growth of Arabidopsis thaliana plantlets was evaluated using an in vitro split system. Arabidopsis fresh weight and total chlorophyll content significantly increased 7 days post-inoculation with the three Metarhizium anisopliae strains evaluated. The primary root length was promoted by all fungal strains without physical contact, whereas in direct contact primary root growth was inhibited. Volatile organic compounds identification revealed that during the interaction of Arabidopsis with Ma-20 and Ma-25 strains only β-caryophyllene was produced, whereas in the Arabidopsis-Ma-28 interaction o-cymene was mainly emitted. The plant growth promoting effect induced by Metarhizium anisopliae strains was also achieved in Arabidopsis, tomato and maize plants grown in soil pots. Our results showed that three Metarhizium anisopliae strains were able to increase plant fresh weight, opening promising perspectives for field production, with the advantages of insect biocontrol and plant growth promotion induced by this species of fungus.


ST2 pathogenetic profile in ambulatory heart failure patients.
Soluble ST2 is involved in multiple pathogenic pathways, including cardiac strain, inflammation, and myocardial necrosis with remodeling. The relative weight of ST2 and the point at which its prognostic value in heart failure (HF) is affected by different degrees of myocardial strain, inflammation, necrosis, and remodeling is unknown. We examined whether soluble ST2 levels improves HF risk stratification relative to other biomarkers representative of multiple pathogenic pathways-N-terminal pro-B-type natriuretic peptide (NT-proBNP; strain), high-sensitivity C-reactive protein (hsCRP; inflammation), and galectin-3 and high-sensitivity troponin T (hsTnT; necrosis and remodeling)-in 1,015 patients with mean left ventricular ejection fraction (LVEF) 33.5%. Mean follow-up was 4.2 ± 2.1 years. The correlation with soluble ST2 was highest with NT-proBNP (r = 0.32; P < .001) and lowest with galectin-3 (r = 0.15; P < .001). ST2 levels increased with increasing concentrations of the other biomarkers (P < .001 in all cases). During follow-up, 467 patients died. Soluble ST2 remained an independent prognosticator of risk at every tertile of each biomarker. This was observed even after adjusting for clinical parameters. Soluble ST2 may be regarded as a 3-in-1 prognosis biomarker in HF. ST2 provides valuable long-term risk stratification information in HF beyond that reported by other biomarkers of stretch, inflammation, necrosis, and remodeling.


[Suggestive guideline for respiratory support in emergency--stepwise breath management].
To propose a guideline of respiratory support for emergency patients. To summarize the experiences gained in giving stepwise respiratory support (SRS) in 2,548 patients for emergency care (including 1,823 trauma patients and 725 non-trauma patients) between 1992 to 2002. There were 1,876 male and 672 female patients with the ratio of male to female 2.79:1. The age of patients ranged between 4 to 86 years, and the mean age of traumatic patients was (32.3+/-19.8) years, and the dominant ages were between 20 to 39. The mean age of non-traumatic patients was (65.2+/-17.3) years, and the dominant ages were between 50 to 69. The traumatic and non-traumatic patients accounted for 60.2% and 32.0% of all patients, respectively. The respiratory management included resuscitation positioning in 816 (32.0%), open airway and suctioning in 314 patients (12.3%), oxygenation through nostril or nasal intubation in 2,311 patients (90.7%), oxygenation by mask in 124 patients (4.9%), endotracheal intubation in 254 patients (10.0%), thyrocricocentesis or cricothyrotomy in 25 patients (1.0%), tracheotomy in 195 patients (7.7%), percutaneous tracheotomy in 58 patients (2.3%). SRW management included two types, four steps and ten ways. The two types included traumatic and non-traumatic; the four steps and ten ways included first step of manual treatment (including (1) resuscitation positioning, (2) open airway and suction and (3) chest-back press), second step oxygenation (including (4) oxygenation through nostril or nasal intubation, (5) oxygenation by mask, (6) endotracheal intubation), third step invasive airway support (including (7) thyrocricocentesis or cricothyrotomy and (8) tracheotomy or percutaneous tracheostomy), fourth step mechanic ventilation (covering (9) manual ventilation and (10) mechanical ventilator). The series of SRS management plan and principles can improve the respiratory support in rescuing emergency patients efficiently.


Volume localized shift selective ¹³C spectroscopy using pulsed rotating frame transfer sequences with windows (PRAWN).
Some novel techniques for volume localized, chemical shift selective (13) C spectroscopy are described in this work. These techniques are based on rotating frame J cross polarization and are reported for both direct and indirect modes of (13) C detection. The performance of two selective mixing sequences, viz., pulsed rotating frame transfer sequences with windows (PRAWN) and PRAWN-π has been studied systematically with different liquid and gel phantoms. Two different front-end modules are used for volume localization, viz., point resolved spectroscopy (PRESS) and localized distortionless enhancement by polarization transfer (LODEPT). It is shown experimentally that both the selective J cross polarization sequences can operate efficiently with very low radiofrequency duty cycle; further, they have considerable tolerance to Hartmann-Hahn mismatch. A simple theoretical analysis is also presented to understand J cross-polarization dynamics at low RF field amplitudes. Finally, the performance of LODEPT-PRAWN-π is demonstrated for the selective detection of saturated fat in pigeon egg in indirect detection mode.


Comparison of pediatric choledochal cyst excisions with open procedures, laparoscopic procedures and robot-assisted procedures: a retrospective study.
The main treatment of choledochal cysts is the complete resection of the cyst with Roux-en-Y hepaticojejunostomy, which includes open procedures, laparoscopic procedures, and robot-assisted procedures using a da Vinci surgical system. The aim of this current study was to investigate the safety and effectiveness of these three different surgical methods in pediatric choledochal cyst excisions. Between January 2015 and December 2018, patients with choledochal cysts treated with open procedures, laparoscopic procedures, or robot-assisted procedures were retrospectively analyzed. The data collected included demographic information of all patients, type and size of cyst, operative details, and postoperative outcomes. A total of 371 episodes of patients were enrolled which consist of the open procedures group (n = 226), laparoscopic procedures group (n = 104), and robot-assisted procedures group (n = 41). The operation time was significantly longer in the laparoscopic procedures group (212.79 ± 34.94) than open procedures group (115.88 ± 13.50) and robot-assisted procedures group (180.61 ± 14.07) (p < 0.001). The volume of intraoperative bleeding were higher in the open procedures group (40.12 ± 55.51) than in the laparoscopic procedures group (21.73 ± 11.44) and robot-assisted procedures group (21.34 ± 9.42), while there was no significant difference between the latter groups. The time to taking water, time to starting liquid diet, and the average length of postoperative hospital stay were similar between the laparoscopic and robot-assisted procedures group, which are shorter than the open procedures group with significant differences. There was no signifcant difference in complications among the three groups. Choledochal cyst excision with robotic-assisted procedures had identical surgical effects as open procedures and had lower technical requirements. But it had higher medical cost and better cosmetic effects. Open procedures had largely positive surgical outcomes with fewest complications but poor cosmetic effects. Laparoscopic procedures were the most technique-demanding approaches with positive cosmetic and economic effect. The incidence of complications of laparoscopic procedures decreased with the learning curve.


Bartonella spp. DNA in cardiac tissues from dogs in Colorado and Wyoming.
Several Bartonella species (spp.) have been identified in dogs diagnosed with infectious endocarditis (IE) or myocarditis. To interrogate cardiac tissues of dogs with suspected IE for the presence of Bartonella spp. DNA of dogs in the Rocky Mountain states. Nine dogs with a clinical diagnosis of endocarditis from January 1990 to June 2008 were included. In this retrospective study, medical records at the Veterinary Teaching Hospital were searched. Animals were excluded if there was no diagnosis of IE in the original necropsy report. Paraffin embedded tissue blocks and medical records were available from 9 dogs. Total DNA was extracted from the cardiac tissues and assessed for Bartonella spp. DNA by 3 polymerase chain reaction (PCR) methods. For positive samples, the Bartonella spp. were determined by genetic sequencing or fluorogenic real-time PCR. Bartonella henselae DNA was amplified from the tissues of 7 dogs; Bartonella vinsonii subsp berkhoffii DNA was amplified concurrently from 3 dogs. Six dogs were from Colorado and 1 was from Wyoming. Flea or tick infestations were reported in 2 dogs. Bartonella spp. should be on the differential list for dogs in the Rocky Mountain states. The results emphasize the need for routine use of external parasite control products even in regions perceived to have low risk for flea and tick infestations.


Colorectal subspecialization in a DGH. The way forward!
To audit all aspects of the diagnosis and management of colorectal cancers by a specialist unit within a District General Hospital (DGH). To compare the clinical effectiveness of the specialist service with the service prior to specialization and attempt to assess the feasibility of setting up such a service within the constraints imposed by a DGH. Data for this study was collected prospectively over a 3-year period from July 1997 to June 2000 since the establishment of a specialist colorectal service. The results so obtained have been compared with the Trent and Wales audit of 1993 as well as with the guidelines issued by the Royal College of Surgeons of England and the Association of Colo-proctologists of Great Britain and Ireland. We have attempted to evaluate whether specialization has altered the outcome for patients with colorectal cancer. A total of 2181 patients were seen at the specialist colorectal clinic and 42% underwent immediate flexible sigmoidoscopy. A total of 241 colorectal cancers were diagnosed during this period by the specialist unit, of which the rapid access clinic had picked up 191 (a pick-up rate of 8.75%). The mean age of patients with colorectal cancer was 69.23 years and the median waiting time from referral to clinic and from referral to treatment was 9 days and 24 days, respectively. These compare favourably with the waiting times prior to specialization. 117 rectal cancers were diagnosed of whom 32 (32%) underwent APER. A selective approach to short course preoperative radiotherapy resulted in 24% of rectal cancer patients receiving this treatment. The CRM was positive in 14% of resected rectal cancers, all of whom had received preoperative radiotherapy. The percentage of patients with Dukes' stage A disease has risen from 11% in 1993 to 23% and the percentage of patients undergoing emergency surgery have fallen from 29% in 1993 to 8.2%. The rate of permanent stoma formation has also decreased from 52% to 32%. This audit has also confirmed that the guidelines for the management of colorectal cancers were all being met or exceeded. The study demonstrates that, even within the constraints of a DGH, a specialist service can result in earlier diagnosis, shorter waiting periods and judicious use of adjuvant treatment leading to improved clinical effectiveness. It is possible to deliver a high quality service, which meets, and in some areas, surpasses the minimum guidelines, provided there is an integrated multidisciplinary approach.


Multimodal treatment of an extremely rare desmoplastic small round cell tumor primary to the brachial plexus - A case report and review of literature.
Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignant neoplasm typically located in the abdomen or pelvis. Other possible locations are the chest, pleura, scrotum, and central nervous system. DSRCT originally arising from the brachial plexus (BP) is extremely rare, to the best of our knowledge, only two cases have been previously described in the English scientific literature. The authors present one new case of DSRCT arising from the left BP, the first in this location with rapid progression and in a female patient. We also highlight the importance of multimodal therapy, which included resection and both adjuvant radiation and chemotherapy. Macroscopic and microscopic characteristics of the lesion are detailed, as well as the patient's status at 56-month follow-up. For primary BP DSRCT, aggressive subtotal resection followed by radiation and chemotherapy can be satisfactory for disease control and for maintaining or improving the neurological status.


Visual outcomes of high-volume compared with low-volume manual small-incision cataract surgery in Nepal.
To study whether manual small-incision cataract surgery (MSICS) in a high-volume setting gives acceptable postoperative visual outcomes. Geta Eye Hospital, Kailali, Nepal. Single-center retrospective study. One-year records of all MSICS in adult patients without any other ocular comorbidity were analyzed retrospectively. Surgical outcomes of cataract cases when surgeons performed more than 72 surgeries (high volume) in a single operating session (1 day) were compared with when fewer than 30 surgeries (low volume) were performed in a single operating session (1 day). Of 23 717 cases in the study, 20 574 patients (87%) had preoperative visual acuity of less than 3/60; 15 632 patients (66%) achieved good visual outcome (uncorrected distance visual acuity of 6/18 or better) postoperatively. Patients operated during high-volume months achieved good visual outcomes in 9930 cases (66.9%) as compared with 5702 (64.3%) in low-volume months. However, 6235 patients (61.7%) operated on during high-volume days had good visual outcomes as compared with 3053 (71.4%) during low-volume days; 175 patients in the high-volume group and 73 patients in the low-volume group (1.7% each) achieved visual acuity worse than 3/60. There were comparable posterior capsular rupture rates (423 [1.78%]) during high- and low-volume months, and 21 cases (0.09%) of postoperative endophthalmitis were noted. MSICS can be used to reduce large cataract backlogs in developing countries as good visual outcomes could be achieved in high-volume settings if standard protocols for quality control are followed.


Cost-effectiveness of tacrolimus ointment in adults and children with moderate and severe atopic dermatitis: twice-weekly maintenance treatment vs. standard twice-daily reactive treatment of exacerbations from a third party payer (U.K. National Health Service) perspective.
A twice-weekly maintenance treatment regimen with tacrolimus ointment for atopic dermatitis (AD) significantly delayed and reduced the number of disease exacerbations over a 12-month period compared with the standard reactive treatment regimen. To determine the cost-effectiveness of tacrolimus ointment used in the maintenance treatment regimen vs. the standard reactive treatment regimen for the management of moderate and severe AD in adults and children. Data from two pivotal phase III studies conducted in adults and children receiving 0·1% and 0·03% tacrolimus ointment, respectively, were used to populate a decision-analytic model. The costs and benefits associated with maintenance vs. reactive use of tacrolimus ointment were calculated over a 12-month period based on the clinical and quality of life data from the clinical trials. The analysis was conducted from the perspective of the U.K. National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. For both adults and children with moderate and severe AD, twice-weekly maintenance treatment with tacrolimus ointment was shown to be a more effective and less costly (dominant) treatment regimen than the standard treatment regimen. Sensitivity analyses demonstrated that the model was robust and largely insensitive to changes in model parameters. Maintenance treatment with tacrolimus ointment for the management of moderate and severe AD provides incremental health benefits at a lower cost compared with the reactive treatment regimen.


Hepatic Sensing Loop Regulates PCSK9 Secretion in Response to Inhibitory Antibodies.
Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9i) lower LDL-C by up to 60% and increase plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels by 10-fold. The authors studied the reasons behind the robust increase in plasma PCSK9 levels by testing the hypothesis that mechanisms beyond clearance via the low-density lipoprotein receptor (LDLR) contribute to the regulation of cholesterol homeostasis. In clinical cohorts, animal models, and cell-based studies, we measured kinetic changes in PCSK9 production and clearance in response to PCSK9i. In a patient cohort receiving PCSK9i therapy, plasma PCSK9 levels rose 11-fold during the first 3 months and then plateaued for 15 months. In a cohort of healthy volunteers, a single injection of PCSK9i increased plasma PCSK9 levels within 12 hours; the rise continued for 9 days until it plateaued at 10-fold above baseline. We recapitulated the rapid rise in PCSK9 levels in a mouse model, but only in the presence of LDLR. In vivo turnover and in vitro pulse-chase studies identified 2 mechanisms contributing to the rapid increase in plasma PCSK9 levels in response to PCSK9i: 1) the expected delayed clearance of the antibody-bound PCSK9; and 2) the unexpected post-translational increase in PCSK9 secretion. PCSK9 re-entry to the liver via LDLR triggers a sensing loop regulating PCSK9 secretion. PCSK9i therapy enhances the secretion of PCSK9, an effect that contributes to the increased plasma PCSK9 levels in treated subjects.


Muscle squeezing immediately after coronary reperfusion therapy using postconditioning with lactate-enriched blood.
We recently reported a new approach for cardioprotection, postconditioning with lactate-enriched blood (PCLeB), and a patient with ST-segment elevation myocardial infarction (STEMI), in whom muscle squeezing of the culprit coronary artery was observed immediately after reperfusion with PCLeB. In this study, we examined the prevalence of muscle squeezing immediately after reperfusion in patients with anterior STEMI treated using PCLeB. PCLeB is a modified postconditioning protocol that comprises intermittent reperfusion and timely coronary injections of lactated Ringer's solution. We treated 30 consecutive patients with anterior STEMI using PCLeB. Among the 30 patients, 4 patients exhibited muscle squeezing of the left anterior descending artery (LAD) immediately after reperfusion. We performed follow-up coronary angiography in 23 patients and found another patient who exhibited muscle squeezing of the LAD. Thus, of 30 patients, 5 were confirmed to have myocardial bridging and 4 exhibited muscle squeezing immediately after reperfusion with PCLeB. No patient died or experienced re-hospitalization for heart failure or recurrent ischemic events at 6 months except for one patient with malignancy. Muscle squeezing immediately after reperfusion therapy is not a rare phenomenon in patients with anterior STEMI treated using PCLeB.


Programs SARGON and DELTA: two new principles for the automated analysis of the visual field.
The new Octopus programs SARGON and DELTA are described. The SARGON program makes possible the arbitrary distribution of a maximum number of 66 test locations with a resolution of up to 0.2 degrees across the 60 degrees visual field. Eighty user-defined self-created programs can be permanently stored and recalled later at will from the program diskette.. The program DELTA evaluates perimetric examination results with the aid of a series of statistical tests and investigates whether the data base is sufficient to assume a significant deviation, or alternatively, whether a visual field defect can be explained simply by spontaneous fluctuations or if a true pathologic defect should be assumed at a particular level of significance. Furthermore, the program tests changes in the visual field as a function of time for their statistical significance.


The effects of melatonin therapy on the treatment of patients with Non-alcoholic steatohepatitis: A systematic review and Meta-analysis on clinical trial studies.
Melatonin has shown promising effects in controlling the progress of non-alcoholic fatty liver disease (NAFLD), introducing it as a possible candidate for NAFLD treatment. In this context, the current study is aimed to evaluate melatonin's effect on the plasma levels of Gamma-glutamyl transpeptidase, cholesterol, triglyceride, and liver aminotransferases in NAFLD patients. NAFLD and melatonin, as well as their related terms, were searched in electronic databases, until May 1st, 2020. The initial search identified 1152 studies. Considering inclusion and exclusion criteria, the final seven articles were included in the study. The methodology of the articles was assessed by the Newcastle-Ottawa Scale. Alanine transaminase levels were significantly lowered with melatonin treatment but not earlier than the 4th week (P = 0.010 and 0.519, respectively). Aspartate aminotransferase levels didn't show significant alteration before 4 weeks, although exhibiting substantial decline in total (P = 0.697 and 0.008, respectively). Alkaline phosphatase changes under 4 weeks of follow-up were not significant (P = 0.3), however, it decreased significantly in total (P = 0.006). A significant decline was detected in triglyceride levels after melatonin treatment (P = 0.015). There was a significant reduction in cholesterol levels (P = 0.005). Gamma-glutamyl transpeptidase levels were also significantly different after the administration of melatonin (P < 0.001). Melatonin could reduce the progress of NAFLD. It might also decrement hepatic function parameters. Thus, it could be used for managing NAFLD and possibly as part of the treatment plan for patients with NAFLD.


A simple method for quantifying ultrasound-triggered microbubble destruction.
Ultrasound-triggered microbubble destruction (UTMD) is essential for targeted drug delivery but currently there is no agreed gold standard for its real-time monitoring. This study used a clinical diagnostic ultrasound scanner to quantify the destruction effects of different values of mechanical index (MI) on microbubble. This was achieved by measuring the signal intensity of peripheral vessels, which is representative of systemic microbubble concentration. Twenty-four male Sprague-Dawley rats and SonoVue contrast agent were used for this study, six for the determination of signal saturation and 18 for the study of microbubble destruction. In the first part of the experiment, four different SonoVue doses (200, 400, 600 and 800 μL/kg) were injected into each of six rats and the signal intensity in their right femoral arteries were recorded using a diagnostic ultrasound scanner. This data was used to plot time-intensity curves (TIC) to determine at which concentration the signal reaches saturation. Then UTMD studies were performed using the 400 μL/kg dose as its peak signal intensity (PSI) was safely within the linear portion of the intensity-concentration curve. The remaining 18 rats were divided into three MI groups (0.2, 0.6 and 1.0) and for each rat, the following was performed: TIC recording of a sham exposure without sonication was performed first using the same scanner from signal saturation study. Simultaneously, another ultrasound scanner was applied to the adductor muscles of left hind limb for sonication later. Then, a sonication TIC recording was performed, with both ultrasound scanners activated. A TIC recording of second sonication was also obtained for comparison. The TICs showed that the area under the curve and the enhancement duration were reduced after sonication in the groups MI = 0.6 and MI = 1.0 but not for the group MI = 0.2. The PSI in the groups with MI of 0.6 and 1.0 were slightly lowered after sonication, although it is not statistically significant. No significant difference of TIC exists between the first and the second sonication for each group. Pharmacokinetic analysis was performed with estimated concentration-time curve derived from TIC curve and found that SonoVue had faster clearance and decreased half-life in the groups MI = 0.6 and MI = 1.0. In conclusion, this study shows that sonographic signal measured from peripheral vessels is a feasible indicator of systemic microbubble concentration and may be used to quantify ultrasound-triggered microbubble destruction at target site.


Complement-pentraxins synergy: Navigating the immune battlefield and beyond.
The complement is a crucial immune defense system that triggers rapid immune responses and offers efficient protection against foreign invaders and unwanted host elements, acting as a sentinel. Activation of the complement system occurs upon the recognition of pathogenic microorganisms or altered self-cells by pattern-recognition molecules (PRMs) such as C1q, collectins, ficolins, and pentraxins. Recent accumulating evidence shows that pentraxins establish a cooperative network with different classes of effector PRMs, resulting in synergistic effects in complement activation. This review describes the complex interaction of pentraxins with the complement system and the implications of this cooperative network for effective host defense during pathogen invasion.


Constructing 3D magnetic flower-like Fe3O4@SiO2@Co3O4@BiOCl heterojunction photocatalyst for degrading rhodamine B.
In this work, the 3D magnetic flower-like Fe3O4@SiO2@Co3O4@BiOCl heterojunction photocatalyst was successfully prepared. The combination of BiOCl with Co3O4 favored to increase specific surface area and separate photo-generated carriers of the resulting composite, resulting in the improvement of catalytic efficiency. The photocatalytic activities of Fe3O4@SiO2@Co3O4@BiOCl were researched in details. In 50 min of visible light, the degradation efficiency for rhodamine B (RhB) of Fe3O4@SiO2@Co3O4@BiOCl was 98.41%. It still maintained 94.22% even after three tests. Furthermore, the photodegradation mechanisms were also investigated, indicating that the improved efficiency was ascribed to the superior separation of photo-induced electron-hole pairs. This study supplies a new perception to fabricate photocatalysts for actual uses.


The Effects of the COVID-19 Pandemic on Mastectomy Outcomes for Breast Cancer.
Single center studies have shown that during the Coronavirus Disease 2019 (COVID-19) pandemic, many patients had surgical procedures postponed or modified. We studied how the pandemic affected the clinical outcomes of breast cancer patients who underwent mastectomies in 2020. Using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database, we compared clinical variables of 31,123 and 28,680 breast cancer patients who underwent a mastectomy in 2019 and 2020, respectively. Data from 2019 served as the control, and data from 2020 represented the COVID-19 cohort. Fewer surgeries of all kinds were performed in the COVID-19 year than in the control (902,968 vs. 1,076,411). The proportion of mastectomies performed in the COVID-19 cohort was greater than in the control year (3.18% vs. 2.89%, <0.001). More patients presented with ASA level 3 in the COVID-19 year vs. the control (P < .002). Additionally, the proportion of patients with disseminated cancer was lower during the COVID-19 year (P < .001). Average hospital length of stay (P < .001) and time from operation to discharge were shorter in the COVID vs. control cohort (P < .001). Fewer unplanned readmissions were seen in the COVID year (P < .004). The ongoing surgical services and mastectomies for breast cancer during the pandemic produced similar clinical outcomes to those seen in 2019. Prioritization of resources for sicker patients and the use of alternative interventions produced similar results for breast cancer patients who underwent a mastectomy in 2020.


Effect of rehabilitation by using the shortened dental arch concept on the thickness of the masseter muscle and occlusal force: A pilot study.
Knowledge of the effect of a shortened dental arch on masseter muscle thickness and occlusal force is sparse but could help clinicians understand how a shortened dental arch might affect the stomatognathic system. The purpose of this pilot clinical study was to evaluate and compare the masseter muscle thickness and occlusal force of participants rehabilitated by using a shortened dental arch with matched completely dentate individuals. Twelve partially edentulous participants with a minimum of 1 posterior occluding pair on each side of the arch were enrolled in the study. The mandibular arch of these participants was rehabilitated by using a single posterior mandibular implant crown (group S). The maxillary arch of all participants in group S was intact. Masseter muscle thickness (cm) and occlusal force (N) were recorded before (T1) and 6 months after implant rehabilitation (T2) for each participant. Twelve participants were selected as controls (group C). They were matched for age, sex, height, and weight with group S and evaluated for masseter muscle thickness and occlusal force. Masseter muscle thickness was evaluated by using ultrasonography during the rest position and maximum volumetric clenching. Occlusal force was measured with an occlusal force measuring appliance. All recordings were done for the left and right sides of the arch. Descriptive analysis was followed by comparison between groups and within group S by using the paired t test (α=.05). Higher masseter muscle thickness and higher occlusal force were observed in group C than in group S before and after rehabilitation. An increase in masseter muscle thickness in the rest position and in maximum volumetric clenching was observed within group S after rehabilitation. Before rehabilitation, a difference in the masseter muscle thickness between group S and group C was statistically significant for the left side at the rest position (P=.017) and during maximum volumetric clenching (P=.016). After rehabilitation, the difference between group S and group C was not statistically significant for masseter muscle thickness at the rest position (P=.890 for right side and P=.555 for left side) and during maximum volumetric clenching (P=.109 for right side and P=.755 for left side). The difference in occlusal force between group S and group C was statistically significant for the right side and left side (P<.001) before rehabilitation and statistically not significant after rehabilitation (P=.161 for the right side and P=.134 for the left side). Rehabilitation following the concept of a shortened dental arch increased masseter muscle thickness and occlusal force in partially edentulous individuals, making the masseter muscle thickness and occlusal force comparable with those of a completely dentate arch.


PDR brachytherapy with flexible implants for interstitial boost after breast-conserving surgery and external beam radiation therapy.
For radiobiological reasons the new concept of pulsed dose rate (PDR) brachytherapy seems to be suitable to replace traditional CLDR brachytherapy with line sources. PDR brachytherapy using a stepping source seems to be particularly suitable for the interstitial boost of breast carcinoma after breast-conserving surgery and external beam irradiation since in these cases the exact adjustment of the active lengths is essential in order to prevent unwanted skin dose and consequential unfavorable cosmetic results. The purpose of this study was to assess the feasibility and morbidity of a PDR boost with flexible breast implants. Sixty-five high risk patients were treated with an interstitial PDR boost. The criteria for an interstitial boost were positive margin or close margin, extensive intraductal component (EIC), intralymphatic extension, lobular carcinoma, T2 tumors and high nuclear grade (GIII). Dose calculation and specification were performed following the rules of the Paris system. The dose per pulse was 1 Gy. The pulse pauses were kept constant at 1 h. A geometrically optimized dose distribution was used for all patients. The treatment schedule was 50 Gy external beam to the whole breast and 20 Gy boost. PDR irradiations were carried out with a nominal 37 GBq 192-Ir source. The median follow-up was 30 months (minimum 12 months, maximum 54 months). Sixty percent of the patients judged their cosmetic result as excellent, 27% judged it as good, 11% judged it as fair and 2% judged it as poor. Eighty-six percent of the patients had no radiogenous skin changes in the boost area. In 11% of patients minimal punctiform telangiectasia appeared at single puncture sites. In 3% (2/65) of patients planar telangiectasia appeared on the medial side of the implant. The rate of isolated local recurrence was 1.5%. In most cases geometrical volume optimization (GVO) yields improved dose distributions with respect to homogeneity and compensation of underdosage at the margins of the implant. Only in 9% of patients was the dose distribution impaired by GVO. However, GVO causes a number of substantial changes of the dose distribution which have consequences for its application. The interstitial CLDR boost of the breast can be replaced by the PDR technique without severe acute and late complications and without deterioration of the cosmetic results.


Regional differences in perceived treatments needs and priorities in relation to antiretroviral therapy among people living with HIV in 25 countries.
While geographic differences in HIV burden are well documented, less is known about regional differences in perceived treatment needs. To fill this gap, the 2019 Positive Perspectives study of people living with HIV (PLHIV) was conducted in 25 countries across Northern America, Latin America, the Asian region, Europe (EU/Schengen countries), Russia, Australia, and South Africa (n = 2389). Overall mean duration of HIV was 10.1 (SD = 9.6) years. The perception that HIV had a negative impact on day-to-day life was lowest among participants from South Africa (14.0%[25/179]) and highest among participants from the Asian region (55.2%[127/230]). Most of the regional gap in the perception that HIV had a negative impact on daily life was explained by regional differences in medication-related unmet needs, stigma, demographic factors, and comorbidities. The percentage who felt they understood their treatment was highest among participants from Australia (87.5%[105/120]) and lowest among those from Russia (62.0%[93/150]), the Asian region (62.2%[143/230]), and South Africa (62.6%[112/179]). Among participants from Northern America, Europe, and Latin America, the treatment goals with the largest absolute increase in perceived importance, from time of starting treatment to time of survey among those diagnosed for ≥1 year, were minimizing the long term impact of antiretroviral treatment and keeping the number of medicines in their antiretroviral regimen at a minimum. Tailored approaches to care of PLHIV are needed as different regions have different disease burden and treatment needs. Equitable approaches to HIV care are needed across and within regions to ensure that patients' unmet needs and preferences are addressed to improve their overall wellbeing and health-related quality of life.