The Impact of Body Mass Index on Postpartum Infectious Morbidities and Wound Complications: A Study of Extremes.
As body mass index increases, the risk of postpartum infections has been shown to increase. However, most studies lump women with a body mass index (BMI) of above 40 kg/m2 together, making risk assessment for women in higher BMI categories challenging. The objective of this study was to evaluate the impact of extreme obesity on postpartum infectious morbidity and wound complications during the postpartum period. The present study is a secondary analysis of women who underwent cesarean delivery and had BMI ≥ 40 kg/m2 in the Maternal-Fetal Medicine Units Cesarean Registry. The primary outcome was a composite of postpartum infectious morbidity including endometritis, wound infection, inpatient wound complication prior to discharge, and readmission due to wound complications. Appropriate statistics used to compare baseline demographics, pregnancy complications, and primary outcomes among women by increasing BMI groups (40-49.9, 50-59.9, 60-69.9, and >70 kg/m2). Rates of postpartum infectious morbidity increased with BMI category (11.7% BMI: 50-59.9 kg/m2; 13.7% BMI: 60-69.9 kg/m2; and 21.9% BMI >70+ kg/m2; p = 0.001). Readmission for wound complications also increased with BMI (3.1% for BMI: 50-59.9 kg/m2; 6.2% for BMI: 60-69.9 kg/m2; and 9.4% for BMI >70+ kg/m2; p = 0.001). After adjusting for confounders, increased BMI of 70+ kg/m2 category remained the most significant predictor of postpartum infectious complications compared with women with BMI of 40 to 49.9 kg/m2 (adjusted odds ratio [aOR] = 6.38; 95% confidence interval [CI]: 1.37-29.7). The adjusted odds of readmission also increased with BMI (aOR = 2.33, 95% CI: 1.35-4.02 for BMI 50-59.9 kg/m2; aOR = 4.91, 95% CI: 2.07-11.7 for BMI of 60-69.9 kg/m2; and aOR = 36.2, 95% CI: 7.45-176 for BMI >70 kg/m2). Women with BMI 50 to 70+ kg/m2 are at an increased risk of postpartum wound infections and complications compared with women with BMI 40 to 49.9 kg/m2. These data provide increased guidance for counseling women with an extremely elevated BMI and highlight the importance of postpartum wound prevention bundles. · Women with super obesity have higher rates of wound complications.. · Women at extremes of obesity experience worse postpartum infectious morbidity.. · More research is needed on effective strategies to minimize morbidity in this population..


Photodynamic therapy in the normal rat colon with phthalocyanine sensitisation.
Photodynamic therapy (PDT) involves the interaction of light with an administered photosensitising agent to produce cellular destruction. It has promising potential for the local and endoscopic treatment of gastrointestinal cancer. There is however little data on the response of normal intestine to PDT. We have investigated the use of a new photosensitiser chloro aluminum sulphonated phthalocyanine (AlSPc) for colonic PDT. The peak concentration of AlSPc in the colon measured by alkali extraction occurred 1 h after i.v. injection. The cellular uptake demonstrated by laser fluorescence microscopy was greater in the mucosa than in the muscle. AlSPc was activated in the tissues by light from an argon ion pumped dye laser at 675 nm. The laser power was set at 100 mW and the fibre placed touching the mucosa. In control animals no macroscopic damage was seen. Temperature measurement using a microthermocouple array showed no temperature rise during light exposure. The energy (fluence), dose of sensitiser and time from sensitisation to phototherapy were altered and the area of necrosis measured. The geometry of the colon made theoretical analysis of the correlation between laser energy and size of lesion difficult. However, following direct measurement of the relative light intensity (fluence rate) in the colon we were able to confirm that there was a threshold fluence for colonic necrosis. The area of photodynamic damage seen 72 h after phototherapy fell with the fall in tissue concentration of AlSPc from 1 h to 1 month after i.v. injection. However, maximum tissue necrosis occurred when treatment was performed immediately after i.v. injection. In this situation, intense vascular spasm was seen and any light transmitted through the colon which fell on the small bowel mesentery caused a lethal ischaemic necrosis. The initial histological changes after PDT were vascular, followed by full thickness necrosis at 72 h. Healing by regeneration was complete by 2-3 weeks. Despite full thickness necrosis there was no reduction in the colonic bursting pressure at any time. Colon treated by hyperthermia had a reduced bursting pressure. Specific collagen stains showed that PDT did not alter the submucosal collagen architecture whereas hyperthermia did.


Neuropsychology of aging.
All people want to age "successfully," maintaining functional capacity and quality of life as they reach advanced age. Achieving this goal depends on preserving optimal cognitive and brain functioning. Yet, significant individual differences exist in this regard. Some older adults continue to retain most cognitive abilities throughout their lifetime. Others experience declines in cognitive and functional capacity that range from mild decrements in certain cognitive functions over time to severe dementia among those with neurodegenerative diseases. Even among relatively healthy "successful agers," certain cognitive functions are reduced from earlier levels. This is particularly true for cognitive functions that are dependent on cognitive processing speed and efficiency. Working memory and executive and attentional functions tend to be most vulnerable. Learning and memory functions are also usually reduced, although in the absence of neurodegenerative disease learning and retrieval efficiency rather than memory storage are affected. Other functions, such as visual perception, language, semantics, and knowledge, are often well preserved. Structural, functional, and physiologic/metabolic brain changes correspond with age-associated cognitive decline. Physiologic and metabolic mechanisms, such as oxidative stress and neuroinflammation, may contribute to these changes, along with the contribution of comorbidities that secondarily affect the brain of older adults. Cognitive frailty often corresponds with physical frailty, both affected by multiple exogenous and endogenous factors. Neuropsychologic assessment provides a way of measuring the cognitive and functional status of older adults, which is useful for monitoring changes that may be occurring. Neuroimaging is also useful for characterizing age-associated structural, functional, physiologic, and metabolic brain changes, including alterations in cerebral blood flow and metabolite concentrations. Some interventions that may enhance cognitive function, such as cognitive training, neuromodulation, and pharmacologic approaches, exist or are being developed. Yet, preventing, slowing, and reversing the adverse effects of cognitive aging remains a challenge.


Could China's long-term low-carbon energy transformation achieve the double dividend effect for the economy and environment?
Exploring the low-carbon energy transformation pathway is vital to coordinate economic growth and environmental improvement for achieving China's carbon peak target. Three energy-target scenarios are developed in this paper, considering the targets of energy structure, electrification rate, and carbon mitigation towards 2030 announced by the Chinese government. A dynamic multi-sectoral computable general equilibrium model, CHINAGEM, is employed to examine the economic and environmental effects under different pathways of long-term low-carbon transformation. It detects that China's energy structure would substantially transfer to the low-carbon and clean one, whereas CO2, SO2, and NOX emissions in 2020-2030 would vastly abate along with all three energy-target scenarios. Different pathways would produce varying positive impacts on China's macro-economy and achieve the different extent of double dividend effects. It is highly conceivable for China to peak its carbon emission at 12.4 GtCO2 by 2028 if it serves the comparatively more stringent low-carbon transformation pathways.


Ciliate ectoparasites (Ciliophora: Trichodinidae/Chilodonellidae) on gills of Carassius auratus from the Yangtze River, China, with the description of Trichodina luzhoues sp. n.
Three species of the genus Trichodina Ehrenberg, 1838 and one species of the genus Chilodonella Strand, 1926 were collected from gills of Carassius auratus. They are Trichodina luzhoues sp. n., Trichodina mutabilis Kazubski and Migala, 1968, Trichodina reticulata Hirschman and Partsch, 1955, and Chilodonella hexasticha Kiernik, 1909. T. luzhoues sp. n. is a medium-sized trichodinid, and its denticles are very distinctive: the blade is narrow rhombus shaped, the section connecting the blade and central part is long and very thin; the section connecting the central part and ray is short and very thick. Ch. hexasticha is a new record in China.


Modular platforms for the assembly of self-adjuvanting lipopeptide-based vaccines for use in an out-bred population.
To facilitate the preparation of synthetic epitope-based self-adjuvanting vaccines capable of eliciting antibody responses in an out-bred population, we have developed two modular approaches. In the first, the Toll-like receptor 2 agonist Pam2Cys and the target antibody epitope are assembled as a module which is then coupled to a carrier protein as a source of antigens to stimulate T cell help. A vaccine candidate made in this way was shown to induce a specific immune response in four different strains of mice without the need for extraneous adjuvant. In the second approach, three vaccine components in the form of a target antibody epitope, a T helper cell epitope and Pam2Cys, were prepared separately each carrying different chemical functional groups. By using pH-mediated chemo-selective ligations, the vaccine was assembled in a one-pot procedure. Using this approach, a number of vaccine constructs including a lipopeptide-protein conjugate were made and also shown to elicit immune responses in different strains of mice. These two modular approaches thus constitute a powerful platform for the assembly of self-adjuvanting lipopeptide-based vaccines that can potentially be used to induce robust antibody responses in an outbred population. Finally, our study of the impact of chemical linkages on immunogenicity of a lipopeptide vaccine shows that a stable covalent bond between Pam2Cys and a B cell epitope, rather than between Pam2Cys and T helper cell epitope is critical for the induction of antibody responses and biological efficacy, indicating that Pam2Cys functions not only as an adjuvant but also participates in processing and presentation of the immunogen.


Fast arc delivery for stereotactic body radiotherapy of vertebral and lung tumors.
Flattening filter-free (FFF) beams with higher dose rates and faster delivery are now clinically available. The purpose of this planning study was to compare optimized non-FFF and FFF RapidArc plans for stereotactic body radiotherapy (SBRT) and to validate the accuracy of fast arc delivery. Ten patients with peripheral lung tumors and 10 with vertebral metastases were planned using RapidArc with a flattened 6-MV photon beam and a 10-MV FFF beam for fraction doses of 7.5-18 Gy. Dosimetry of the target and organs at risk (OAR), number of monitor units (MU), and beam delivery times were assessed. GafChromic EBT2 film measurements of FFF plans were performed to compare calculated and delivered dose distributions. No major dosimetric differences were seen between the two delivery techniques. For lung SBRT plans, conformity indices and OAR doses were similar, although the average MU required were higher with FFF plans. For vertebral SBRT, FFF plans provided comparable PTV coverage, with no significant differences in OAR doses. Average beam delivery times were reduced by a factor of up to 2.5, with all FFF fractions deliverable within 4 min. Measured FFF plans showed high agreement with calculated plans, with more than 99% of the area within the region of interest fulfilling the acceptance criterion. The higher dose rate of FFF RapidArc reduces delivery times significantly, without compromising plan quality or accuracy of dose delivery.


Left Ventricular Regional Function in Children with Beta Thalassemia with No Cardiac Manifestations (Four-Dimensional Echocardiographic Study).
Early detection of myocardial dysfunction is essential for the management of patients with thalassemia. Four-dimensional echocardiography imaging technique may be useful for detecting subclinical cardiovascular disease. To evaluate the 4-dimensional echocardiographic strain in children with beta thalassemia major with no cardiac manifestation and correlate it with other echocardiographic parameters. This is a prospective cross-sectional cohort Study included 200 children, 1-18 years-old. They were divided into: One hundred children with p-Thalassemia major with no clinical cardiac manifestations and 100 healthy children as a control group. They were subjected to the following investigations: Complete blood count, serum ferritin and Four-dimensional echocardiographic strains (Longitudinal, Circumferential, Radial and Area strains). There was no significant difference between the two groups as regard mitral annulus systolic velocity (S wave), E/A ratio and iso-volumic acceleration, but there was a significant difference as regard to ejection fraction, left ventricle mass, sphericity index and myocardial performance index. The mean values of Left Ventricular Strains (Longitudinal, Circumferential, Radial and Area strains) were significantly lower in patients with thalassemia (- 14.86 ± 12.13, - 8.01 ± 3.829, 33.13 ± 10.61, - 19.45 ± 6.866) than controls (- 19.13 ± 1.502, - 16.32 ± 1.34, 37.28 ± 4.209, - 22.94 ± 3.06) than controls respectively with a positive correlation with 2-Dimensional strain. Strain parameters of the left ventricle obtained by four-dimensional.


Molecular epidemiological study of Pseudomonas aeruginosa isolates from patients with acute leukemia.
In an attempt to determine the genetic relationship between strains of Pseudomonas aeruginosa isolated from patients with acute leukemia, a recently described restriction fragment from the region upstream of the exotoxin A structural gene was used as a probe in Southern hybridization. The overall rate of cultures positive for Pseudomonas aeruginosa during 169 admissions (119 patients) was 17%. Twelve genotypically distinct strains were found among 18 colonized and/or infected individuals. Three of these strains were recovered from more than one patient, suggesting a certain risk of nosocomial transmission of Pseudomonas aeruginosa and cross-infection. Genotypic comparison showed identical restriction patterns in multiple isolates from single patients, and also in colonizing and subsequently infecting strains. Genotyping distinguished isolates with similar O serotypes and established the identity between isolates with differing susceptibility to agents used for antibacterial prophylaxis.


Electron capture at the iron-oxygen centre in single crystals of oxymyoglobin studied by electron spin resonance spectroscopy.
Exposure of single crystals of oxy-myoglobin to 60Co gamma-rays at 77 K results in electron addition to the Fe-O2 units. The resulting ESR spectrum has been analysed to give the principal values and directions for the g-tensor of this unit. The results suggest that the dioxygen ligand is strongly tilted, the direction of tilt being close to one of the bisectors of the N-Fe-N bond angles. Possible reasons for this orientation are discussed.


My, what asthenia you have.
A 59-year-old woman noted intermittent ptosis, diplopia, dysphagia, and proximal muscle weakness for several years. She had a strong family history of myasthenia gravis. Chest computed tomography and sternotomy revealed a micronodular spindle cell thymoma. Electromyography and antibody testing was negative for myasthenia gravis. Genetic testing confirmed a diagnosis of oculopharyngeal muscular dystrophy.


Psychometric properties of the anxiety sensitivity index-3 in an acute and heterogeneous treatment sample.
Anxiety sensitivity (AS) is associated with various forms of psychopathology. The most common measure of AS is the anxiety sensitivity index-3 (ASI-3). The current study examined the psychometric properties and factor structure of the ASI-3 in an acute and comorbid population seeking treatment for a broad range of psychopathology (N=382). Results confirmed a bi-factor structure and suggested that the ASI-3 demonstrates adequate psychometric properties in a transdiagnostic sample. The ASI-3 also showed adequate sensitivity to change over the course of partial hospital treatment. Findings regarding associations between specific anxiety disorders and subscales of the ASI-3 are discussed. Overall, the current results support the use of the ASI-3 to assess AS in heterogeneous treatment-seeking samples. This work is of particular utility for researchers examining the concept of AS transdiagnostically.


Desire for thinness among young Japanese women from the perspective of objective and subjective ideal body shape.
I examined the actual situation of the desire to be thin among young Japanese women from the perspective of ideal body shape and actual measured body shape. In total, 90 young Japanese women were evaluated using a questionnaire (perceived body shape and desired body composition change) and assessments of sarcopenia (muscle strength, physical ability, and muscle mass). Participants were classified into the underweight (body mass index [BMI] < 18.5 kg/m2, 74%), normal-weight (18.5 ≤ BMI < 25 kg/m2, 20%), or obese (25 ≤ BMI < 30 kg/m2, 6%) groups. The normal-weight group needed to gain an average of 2.2 kg to reach the objective ideal weight, but participants desired to lose an average of 4.5 kg. The underweight group needed to gain an average of 10.3 kg to reach the objective ideal weight, but participants desired to maintain their current body weight. Data on muscle mass for the diagnosis of sarcopenia showed low values for the underweight group. Most participants were classified into the normal-weight and underweight groups, but these groups showed a high percentage of women with a desire to be thin. The body shape of young adult women should be carefully considered not only as a health issue of thinness during the fertile period but also as a countermeasure to sarcopenia (low skeletal muscle mass) during the aging process.


Depression, Anxiety and Stress Among Indians in Times of Covid-19 Lockdown.
Covid-19 has caused significant distress around the globe. Apart from the evident physical symptoms in infected cases, it has caused serious damage to public mental health. India, like other countries, implemented a nationwide lockdown to contain and curb the transmission of the virus. The current research is an attempt to explore psychological distress among people residing in India during the lockdown. Four hundred and three participants were asked to complete a questionnaire with questions around symptoms of depression, anxiety, stress, and family affluence. The results indicated that people who do not have enough supplies to sustain the lockdown were most affected, and family affluence was found to be negatively correlated with stress, anxiety, and depression. Among different professions, students and healthcare professionals were found to experience stress, anxiety, and depression more than others. Despite the current situation, stress, anxiety, and depression were found to be in normal ranges for mental health professionals highlighting their capabilities to remain normal in times of distress. Policymakers and other authorities may take the assistance of mental health professionals to help overcome psychological issues related to Covid-19.


A comparison of duration of first prescribed insulin therapy in uncontrolled type 2 diabetes.
We investigated whether differences in duration of first insulin use in type 2 diabetes remain after adjustment for potential confounders, and what factors are associated with longer use. People prescribed a first insulin (2000-2007) after 2-3 non-insulin glucose lowering treatments (OGLD) were identified from the THIN UK primary care database and grouped by insulin, detemir (n=165), glargine (n=1011) or NPH (n=420). Time from beginning insulin to the prescription of another insulin type or a glucagon-like peptide was compared between insulins in a Cox model adjusting for: demographics, HbA1c, history of vascular complications and cardiovascular risk factors. The strength of association between duration of use and these variables was investigated. The adjusted hazard ratios compared to glargine for treatment change were 1.58 (95% CI 1.25, 2.00) for detemir and 1.49 (1.25, 1.78) for NPH. Lower mean treatment HbA(1c) correlated with longer time to a different insulin regimen (Spearman rank correlation -0.30, p<0.01) as were continuing OGLDs, older age, longer time from diagnosis, lower body mass index, lower HbA(1c), and no heart failure at baseline. People who began treatment with glargine and those with better on-treatment HbA(1c) remained on their first insulin for longer than those who began detemir or NPH.


CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.
Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.


The effectiveness of different concentrations of chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis.
To evaluate the effectiveness of chlorhexidine for the prevention of ventilator-associated pneumonia and explore the preferred concentration of chlorhexidine. The implementation of effective oral care measures could reduce the incidence of ventilator-associated pneumonia, but among several randomised controlled trials, whether using chlorhexidine is effective and which concentration is more appropriate remain controversial. A meta-analysis was conducted. We searched the Cochrane Library, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, China Biology Medicine disc and Chinese National Knowledge Infrastructure to collect randomised controlled trials of mechanically ventilated adult patients receiving oral care with chlorhexidine to prevent ventilator-associated pneumonia. The quality of randomised controlled trials was critically appraised, data were extracted by two reviewers independently, and disagreement was resolved by consensus. Meta-analyses were conducted for the eligible randomised controlled trials by revman 5.1. Relative risks and 95% CIs were calculated with the Mantel-Haenszel model, and heterogeneity was assessed with the I(2) test. Eighteen randomised controlled trials were included and a meta-analysis was used. All studies indicated chlorhexidine could significantly prevent and reduce the incidence of ventilator-associated pneumonia [RR = 0·59, 95% CI (0·50-0·69), p < 0·00001]. Nine studies showed 0·12% chlorhexidine had a significant effect [RR = 0·53, 95% CI (0·43-0·67), p < 0·00001]. Three studies proved the effect of the 2% chlorhexidine on the prevention of ventilator-associated pneumonia [RR = 0·55, 95% CI (0·37-0·81), p = 0·002]. Chlorhexidine can prevent and reduce the incidence of ventilator-associated pneumonia. Chlorhexidine of 0·12% has the best effect on the prevention of ventilator-associated pneumonia according to the meta-analysis, cost analysis, adverse reactions and drug resistance analysis. Ventilator-associated pneumonia remains a leading cause of morbidity and mortality in intensive care unit, and implementing effective oral care can reduce the incidence of ventilator-associated pneumonia. Chlorhexidine of 0·12% is recommended in our study.


Flexible Electronics: An Epidermal Stimulation and Sensing Platform for Sensorimotor Prosthetic Control, Management of Lower Back Exertion, and Electrical Muscle Activation (Adv. Mater. 22/2016).
The design of an ultrathin, conformal electronic device that integrates electrotactile stimulation with electromyography, temperature, and strain sensing in a single, simple platform is reported by J. A. Rogers and co-workers on page 4462. Demonstrated application possibilities include prosthetic control with sensory feedback, monitors, and stimulation signals related to lower back exertion, and electrical muscle stimulation with feedback control.


PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling.
Neurons and oligodendrocytes are produced in the adult brain subventricular zone (SVZ) from neural stem cells (B cells), which express GFAP and have morphological properties of astrocytes. We report here on the identification B cells expressing the PDGFRalpha in the adult SVZ. Specifically labeled PDGFRalpha expressing B cells in vivo generate neurons and oligodendrocytes. Conditional ablation of PDGFRalpha in a subpopulation of postnatal stem cells showed that this receptor is required for oligodendrogenesis, but not neurogenesis. Infusion of PDGF alone was sufficient to arrest neuroblast production and induce SVZ B cell proliferation contributing to the generation of large hyperplasias with some features of gliomas. The work demonstrates that PDGFRalpha signaling occurs early in the adult stem cell lineage and may help regulate the balance between oligodendrocyte and neuron production. Excessive PDGF activation in the SVZ in stem cells is sufficient to induce hallmarks associated with early stages of tumor formation.


Mastitis and its impact on structure and function in the ruminant mammary gland.
It is a given in biology that structure and function go hand-in-hand. At the level of the mammary alveoli, copious milk production depends on the proliferation of mammary epithelial cells and the biochemical and structural differentiation of these cells after parturition. For example, data from quantitative structural studies demonstrate that differences in milk production between beef and dairy cows correspond with a relative failure of alveolar cell differentiation in cattle not specifically selected for milk yield. It is likely, but not proven, that production differences within or between dairy breeds are also determined by differences in the capacity of alveolar cells to differentiate or to maintain an adequate state of differentiation. These observations strongly support the belief that insults from mastitis that lead to losses in mammary function are directly related to disruption of alveolar cell integrity, sloughing of cells, induced apoptosis, and increased appearance of poorly-differentiated cells. Ironically, reduced milk production in cases of subclinical mastitis, is also associated with increases in milk somatic cell count. Thus the elevated neutrophil migration evoked to fight inflammation can inadvertently rendered alveolar epithelial cells non-secretory. A challenge to future researchers will be to devise mastitis treatments and therapies that prevent and/or repair damage to alveolar structure and maximize subsequent secretory cell differentiation.


[Structural transformations of the vascular system of the connective tissue layer of the skin].
Electron microscopic radioautography was performed in skin biopsies obtained from six surgical patients without skin lesions. It has been discovered that besides typical vessels--arterioles and venules--there are vessels with damaged structure in connective tissue of skin basis. On serial electron microscopic sections vascular wall thinning and gradual disconnection of wall-forming cells can be visualized. The authors suggest that structural changes in connective tissue vessels of skin basis are the physiological phenomenon. As a result of such changes pericytes may separate from the vascular wall and initiate new populations of fibroblasts.


Polyamine metabolism and interconversion in NIH 3T3 and ras-transfected NIH 3T3 cells.
The effect of transfection of NIH 3T3 cells by the human ras (c-Ha-ras-1) oncogene on uptake, interconversion, and excretion of polyamines was studied. Uptake and interconversion of spermidine were higher in the ras-transfected cells. Acetylpolyamines were excreted into the medium by the ras-transfected cells, whereas they were retained by NIH 3T3 cells. In addition to acetylpolyamines, some unknown polyamine conjugates occurred in the ras-transfected cells.


Visual outcomes with femtosecond laser-assisted cataract surgery versus conventional cataract surgery in toric IOL insertion.
To evaluate the visual outcomes of femtosecond laser-assisted cataract surgery (LCS) compared with phacoemulsification cataract surgery (PCS) in patients undergoing Toric IOL insertion. A non-randomized, single surgeon, prospective, comparative cohort case series PARTICIPANTS: Patients undergoing LCS and PCS between January 2012 and July 2014 at a single center. The LCS group underwent femtosecond laser pretreatment for the anterior capsulotomy and lens fragmentation. Otherwise standard phacoemulsification surgery and foldable toric intraocular lens insertion proceeded. Best corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), pre and post operative cylinder and mean absolute refractive error. A total of 418 eyes from 323 patients were included in the study; with 95 eyes in the PCS group and 323 in the LCS group. There were 243 (75.5%) LCS eyes with a pre-operative BCVA of 20/40 or better and 54 (56.8%) in the PCS group (p < 0.001). For post-operative BCVA, 315 (97.5 %) LCS and 81 (85.3%) PCS eyes had a BCVA of 20/40 or better (p = <0.001). However, there was no significant difference for change in BCVA between the groups (mean gain in EDTRS letter 11.0 for LCS and 10.3 for PCS p = 0.64) or in MAE (mean 0.56D PCS vs 0.65D LCS p = 0.18). In patients receiving toric intraocular lenses, there is similar improvement in terms of letters gained with LCS and PCS. Overall, there is no additional benefit for patients undergoing LCS in this cohort.


Nurses' compliance with prevention of mother-to-child transmission national guidelines in selected sites in Kinshasa, Democratic Republic of Congo.
The Democratic Republic of Congo (DRC) implemented a prevention of mother-to-child transmission (PMTCT) of HIV infection programme in maternal, newborn and child health (MNCH) services in 2001 with nurses as key personnel. To date there is no information in the DRC and specifically in Kinshasa with respect to compliance with PMTCT national guidelines. The study aimed at describing nurses' compliance with the PMTCT national guidelines in selected PMTCT sites of Kinshasa. A descriptive cross-sectional study was conducted in Kinshasa with 76 nurses in 18 selected PMTCT sites. The nurses' compliance with PMTCT national guidelines was assessed using a healthcare provider self-reporting questionnaire developed by the researchers. The study showed that the mean score of nurses' compliance with PMTCT national guidelines was 74% (95% CI: 69%-78%) which progressively decreased and was significantly different across different MNCH services (p = 0.025). With respect to categories of PMTCT recommendations, nurses were compliant with those related to education in labour and delivery, and antenatal services. Sociodemographic characteristics such as training, length of service and category of nurses did not influence nurses' compliance score. These findings showed that nurses were noncompliant with PMTCT national guidelines, with the score level being 80% or more in the three MNCH services/units. Improvement of nurses' 'compliance with the PMTCT national guidelines requires effective monitoring of full integration of PMTCT as routine activities in MNCH care.


Rapid consecutive three-component coupling-Fiesselmann synthesis of luminescent 2,4-disubstituted thiophenes and oligothiophenes.
(Hetero)aroyl chlorides, alkynes, and ethyl 2-mercapto acetate can be reacted in a consecutive three-component synthesis to give 2,4-disubstituted thiophene 5-carboxylates in good to excellent yields. In the sense of a pseudo-five-component reaction highly blue luminescent symmetrical terthiophenes and a quinquethiophene can be synthesized in excellent yield.


A prospective comparison of total knee arthroplasty using ultra-congruent, condylar-stabilizing, and posterior-stabilized devices implanted with kinematic alignment: better 2-year outcomes with ultra-congruent.
This study compared the 5-year results of posterior cruciate ligament (PCL)-sacrificing total knee arthroplasty (TKA) with either a post and cam posterior-stabilized (PS) device, a dished, congruent condylar-stabilizing (CS) device, or a deep-dished ultra-congruent (UC) device. The hypothesis was that the clinical and radiographic outcomes would be equivalent. CS and PS participants were part of a prospective, randomized trial, and UC participants were part of a separate prospective, non-randomized protocol that was otherwise identical. A kinematic alignment surgical technique was utilized. Participants were assessed preoperatively, and postoperatively at 6 weeks, 6 months, and annually for 5 years by Knee Society Score (KSS), SF-36 v2, Lower Extremity Activity Scale (LEAS), and physical and radiographic evaluation. There were 116 CS/PS participants and 69 UC participants who participated in the study. Tourniquet (P = .02) and operative (P = .01) times for the CS and UC groups were significantly shorter than the PS group. KSS Function scores were better for the UC group than the CS and PS groups at 6 months (P = .04) and 1 year (P = .03), and better in the UC group vs. CS at 2 years (P = .04). The KSS Pain-only score was also better in the UC compared to PS at 6 months (P = .04). There were no significant differences for the KSS Pain/Motion scores, flexion, SF-36, and LEAS scores at any time. These data confirm the hypothesis that there are no clinically meaningful significant differences in outcomes between the three groups at a 5-year minimum follow-up, though there is a trend toward less pain and better function at earlier visits in the UC group. II.


Impact of mandibular condyle preservation on patterns of failure in head and neck cancer.
To determine the role of native condyle preservation in local recurrence after segmental mandibulectomy in patients with head and neck squamous cell carcinoma. Retrospective chart review with main outcome measuring local control of cancer. Between 1994 and 2003, 72 patients (48 men, 24 women) with an average age of 73.5 years without previous treatment underwent segmental mandibulectomy. Fifty-four cases (n = 54) involved the mandible posterior to the mental foramen and are the subject of this review. In 36 patients, the condyle was preserved and mandibular continuity was restored. In 18 patients, condyle and ramus were resected without mandibular reconstruction. Reconstructive modalities included primary closure (3), split-thickness skin graft (3), pedicle flap (19), and free tissue reconstructions (29). Overall local-regional recurrence rate was 22 percent (12 of 54); no recurrences were identified in patients who underwent condylar resection. Recurrences were observed in patients with mandibular reconstruction by both plate and pedicle flap (5 of 9) or (osteo) myocutaneous free flap (7 of 27). Condylar preservation may predispose patients to local recurrence after segmental mandibulectomy. This does not translate into overall reduction in survival.


Examining gender, racial, and age differences in weight concern among third, fifth, eighth, and eleventh graders.
Weight management and concern, body weight beliefs, and perceptions of friend's and family's weight concerns were examined in this study by race, grade, and gender. A stratified random sample was used to select schools within nine districts in South Carolina and an anonymous self-report paper-pencil questionnaire was completed by the students. The final sample included 3151 African American (42.3%) and White (57.7%) children (51.7% female) in the third (n=599), fifth (n=686), eighth (n=1168), and eleventh (n=698) grades. White girls were more likely to report being overweight (P=.0042), having higher personal weight concerns (P<.0001), and perceiving higher friend (P<.0001) and family weight concerns (P<.0001) than the African American girls. Using multiple regression, 29.8% of the variance in the children's personal weight concern scores was explained by perceptions of family's weight concerns (R(2)=.1659), gender (R(2)=.0762), perceptions of friend's weight concerns (R(2)=.0392), grade (R(2)=.0094), a Race x Gender interaction (R(2)=.0042), and race (R(2)=.003). Most of the children, particularly the white girls, have personal weight concerns and dieting practices which place them at risk for possible health problems. These results support the need for nutrition interventions and education in early childhood. Programs to prevent obesity and eating disorders should be tailored for differences by gender, grade, and race.


Outcomes of Incidental Appendectomy During Ovarian Operations in a National Pediatric Cohort.
The utility of incidental appendectomy (IA) during many ovarian operations has not been evaluated in the pediatric population. This study sought to compare outcomes after ovarian surgery with IA in the pediatric population. Females (≤20 y old) undergoing ovarian surgeries (oophorectomy, detorsion and/or drainage) were identified from the Nationwide Readmissions Database (2016-2018). Those with appendicitis were excluded. A propensity score-matched analysis (PSMA) with 46 covariates (demographics, comorbidities, hospitalization factors, etc.) was performed between those receiving ovarian surgery with or without IA. There were 13,202 females (median age 17 [IQR 14-20] y old) who underwent oophorectomy (90%), detorsion (26%), and/or ovarian drainage (13%). There were more episodes of torsion in the PSMA cohort receiving ovarian surgery alone (17% versus 10% IA; P = 0.016), while other indications (ovarian mass, cyst) were similar. Open (66% versus 34% laparoscopic) IAs were more frequent. Length of stay (LOS) was longer for those undergoing IA (3 [2-4] versus 2 [2-4] days ovarian surgery alone; P < 0.001). There was a higher rate of postoperative GI complications in the IA cohort. Subgroup analysis of those undergoing laparoscopic operations demonstrated no difference in LOS or postoperative complications between patients undergoing IA or not. These data indicate that IA in pediatric ovarian operations is associated with longer LOS and higher GI postoperative complications. However, laparoscopic IA was not associated with higher cost, complications, LOS, or readmissions. This suggests that IA performed during ovarian surgeries in select patients may be cost-effective and worthy of future study.


Empagliflozin attenuates trastuzumab-induced cardiotoxicity through suppression of DNA damage and ferroptosis.
Trastuzumab (TZM) is commonly used for target therapy in breast cancer patients with high HER2 although the cardiotoxicity restricts its clinical usage. DNA damage and ferroptosis are implicated in anti-tumor drug cardiotoxicity. Given the emerging use of SGLT2 inhibitors in clinical cardiology, this study evaluated the impact of SGLT2 inhibitor Empagliflozin on TZM-induced cardiotoxicity, and mechanism involved with a focus on DNA damage and ferroptosis. Adult C57BL/6 mice were challenged with TZM (10 mg/kg/week, i.p.) or saline for six weeks. A cohort of mice received Empagliflozin (10 mg/kg, i.p.) at the same time. Myocardial function, morphology, ultrastructure, mitochondrial integrity, oxidative stress, DNA damage and various cell death domains were evaluated in TZM-challenged mice with or without Empagliflozin treatment. Our data revealed that TZM challenge overtly increased levels of serum LDH and troponin I, promoted adverse myocardial remodeling (increased heart weight, chamber size, cardiomyocyte area and interstitial fibrosis), contractile dysfunction and intracellular Ca2+ mishandling, oxidative stress, lipid peroxidation, mitochondrial ultrastructural damage, DNA damage, apoptosis and ferroptosis, the effects of which were greatly attenuated or mitigated by Empagliflozin with little effects from Empagliflozin itself. In vitro study indicated that induction of DNA damage mimicked TZM-induced lipid peroxidation and cardiomyocyte contractile dysfunction while the ferroptosis inducer erastin mitigated Empagliflozin-offered protection against lipid peroxidation and cardiomyocyte dysfunction (but not DNA damage). Likewise, in vivo and in vitro inhibition of ferroptosis recapitulated Empagliflozin-offered cardioprotection against TZM exposure. Taken together, these data demonstrated that Empagliflozin may be possible candidate drug for TZM cardiotoxicity likely through a DNA damage-ferroptosis-mediated mechanism.


Maternal organic selenium supplementation during gestation enhances muscle fiber area and muscle fiber maturation of offspring in porcine model.
Organic selenium supplementation during gestation improves the antioxidant status and reproductive performance of sows and increases the antioxidative capacity of the intestines of their offspring. This study was conducted to investigate the effect of maternal basel diet (control) supplemented with an organic Se, 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), or inorganic sodium selenite (Na2SeO3) during gestation on the antioxidant status and development of muscle in newborn and weaned piglets. Newborn piglets before colostrum intake and weaned piglets were selected for longissimus dorsi (LD) muscle collection and analysis. The results showed that maternal HMSeBA supplementation increased the muscle area and content of Se in the LD muscle of newborn piglets, improved gene expression of selenoproteins, and decreased oxidative status in the LD muscle of both newborn and weaned piglets compared with the control. The expression of muscle development-related genes of newborn piglets in the HMSeBA group was lower than in the control group, whereas the expression of MRF4 in weaned piglets was higher in the HMSeBA group than in the control and Na2SeO3 groups. In addition, HMSeBA supplementation decreased the mRNA expressions of myosin heavy chains (MyHC) IIx and MyHC IIb and the percentage of MyHC IIb; increased the expression of PGC-1α in the LD muscle of newborn piglets; increased the gene expression of MyHC IIa; and decreased the protein expression of slow MyHC and the activity of malate dehydrogenase in the LD muscle of weaned piglets compared with the control group. Maternal HMSeBA supplementation during gestation can improve the antioxidative capacity of the muscle of their offspring and promote the maturity of muscle fibres in weaned offspring.


The event study in international business research: Opportunities, challenges, and practical solutions.
The event study or event study method (ESM) is an empirical technique for capturing investors' reaction to an event affecting one or more publicly traded firms. The ESM has been little employed in international business (IB) research despite its frequency in accounting, economics, and finance; for example, only two percent of the empirical articles in JIBS over 1970-2019 include an event study. While this scarcity could indicate a lack of demand, we argue that the field of IB studies offers many interesting and important research opportunities for an event study. We believe that the challenges arise primarily from the supply side, because conducting an event study involves overcoming a variety of data and analytical hurdles. We examine these methodological challenges and offer practical solutions designed to encourage adoption of the ESM. An online appendix with coding and examples provides additional resources. The online version contains supplementary material available at 10.1057/s41267-022-00509-7.


Characteristics of cardiac aging in C57BL/6 mice.
The specific processes that cause aging of the cardiac tissue remain elusive. C57BL/6 (B6) mice are commonly used for investigating age-related diseases in mammals. We thus sought to evaluate the cardiac aging process in B6 mice. Cardiac tissues from the newborn (B6 NB), 2month-old (B6 2M) and 21-27month-old B6 mice (B6 aged) were used for the investigation. Several age-related cellular processes were evaluated, including telomere shortening, changes in p53 and p16 expression, changes in mitochondria DNA expression and DNA deletion, and alteration of mitochondria. We found that the aging of the B6 mice cardiac tissue is associated with the maintenance of telomere length, increased expression of p53 and p16, mild changes in mitochondrial DNA expression but widespread DNA deletion, and significant alterations of the mitochondrial ultrastructure within the cardiac tissue. The results of our studies suggest that mitochondrial DNA deletions, which affect the mitochondrial ultrastructure, cytochrome C oxidase activity, and p53 expression, are significantly associated with cardiac aging and may be a source of age-related heart failure.


Reinforcing apoptosis-resistance of COS and myeloma cells by transfecting with bcl-2 gene.
COS, myeloma and HeLa cells, which are commonly used for protein production by cell culture, were transfected with human bcl-2 gene encoded on the shuttle vector BCMGS. Expression of human bcl-2 improved survival of cells remarkably, mildly, or negligibly for COS, myeloma, and HeLa, respectively. Four clones were obtained from the human bcl-2 expressing cell population of COS cells. They expressed human bcl-2 almost at the same level. The viable cell numbers were 6, 2.5, 2.5, and 0.8 times as many for the clones #8, #5, #6, and #7, respectively, as for the control COS cells, when they were cultured at low (0.2%) serum concentration for 9 days. The bcl-2 overexpressing COS cells showed morphology different from that of the control COS cells in serum limited condition. When transfected with mouse lambda protein gene carried by an SV40-derived vector, clone #8 of the bcl-2 transfected COS cells continued the transient expression of lambda protein longer than the control COS cells.


Enantioselective 1,4-Addition Reaction of α,β-Unsaturated Carboxylic Acids with Cycloalkanones Using Cooperative Chiral Amine-Boronic Acid Catalysts.
An enantioselective 1,4-addition of α,β-unsaturated carboxylic acids with cycloalkanones has been developed by using chiral amine-boronic acid cooperative catalysts. In the presence of a chiral amine and boronic acid, cycloalkanones and carboxylic acids are activated as chiral enamines and mixed anhydrides, respectively. The corresponding 1,4-adducts are obtained in high yield with high enantioselectivity. Furthermore, subsequent oxylactonization of the 1,4-adducts gives spirolactones with high diastereoselectivity.


Comparison of dinucleotide frequency and codon usage in Toxoplasma and Plasmodium: evolutionary implications.
The weight-averaged observed/expected dinucleotide frequencies for the sum total of the coding regions of five Toxoplasma genes were compared with the same parameters previously determined for the coding regions of 21 Plasmodium genes. In addition, codon usage in the five Toxoplasma genes was compared with that in the 21 Plasmodium genes, and the percent distribution of amino acids in the Toxoplasma protein pool and the Plasmodium protein pool were compared with that in a general protein pool of 314 proteins. The results are consistent with the hypothesis that, contrary to currently held opinion, the genera Toxoplasma and Plasmodium are not especially closely related.


Development and psychometric validation of a novel measure of sensory expectancies associated with E-cigarette use.
E-cigarette dependence measures largely focus on e-cigarette use ("vaping") that is linked to nicotine use, and measures assessing sensory aspects of vaping that may influence use (e.g., taste) are limited in scope. Thus, we developed the novel Sensory E-cigarette Expectancies Scale (SEES). In Summer 2017, 610 adult e-cigarette users (48.7% male, 84.9% White, 37.41[±12.15] years old) completed an online survey that included 23 SEES items. Psychometric analyses included evaluating latent structure, internal consistency, measurement invariance, mean differences, and test-criterion relationships. Factor analyses supported a 9-item, 3-subscale structure (taste/smell, pleasure/satisfaction, vapor cloud production). Subscales evidenced internal consistency and scalar invariance by sex, race, smoking status (current/not), vaping status (daily/not), e-liquid nicotine content (yes/no), and device type (cig-a-likes/vape-pens/Advanced Personal Vaporizers [APVs]/Mods). Women and daily e-cigarette users reported stronger SEEs for taste/smell and pleasure than their counterparts. Non-white participants reported stronger SEEs for cloud production than White participants. Cig-a-like users reported the weakest SEEs for taste/smell and weaker SEEs linked to cloud production than APV/mod users. SEES scores evidenced convergence with nicotine dependence (mean r = .36). Finally, SEES scores predicted vaping frequency and habitual vaping concurrently and incrementally beyond nicotine dependence. The SEES evidenced good psychometric properties, suggesting that the measure can be used to assess sensory vaping expectancies in adults. Importantly, SEES scores indicated that sensory expectancies are related, yet distinct, from nicotine dependence. Future research should evaluate how SEEs relate to product characteristic preferences and patterns of vaping including the development and maintenance of addiction.


Importance of electromyographic data in interpreting nocturnal penile tumescence.
The use of home monitoring of nocturnal penile tumescence has potential advantages if it can reliably replace full somnographic recording. However, little is known of the relationship between home monitoring and full somnographic recording. The present study compared 26 records from 13 patients. Each record was scored independently by two evaluators, and the results indicate that home monitoring can lead to overestimation of NPT and errors in etiologic diagnosis.


Factors affecting the TMPTA radical polymerization photoinitiated by phenyltrialkylborates paired with tri-cationic hemicyanine dye. Kinetic studies.
This article introduces tri-cationic hemicyanine dye employed as a visible-light photoinitiator of acrylic monomers polymerization. This dye, in combination with borate anions, was found to be a very effective photoinitiating system. The kinetics of trimethylolpropane triacrylate polymerization was studied by a microcalorimetric method. The photoredox pair concentration, the co-initiator structure as well as the light intensity strongly affected the progress of the polymerization, leading, for example, to an increase in the polymerization rate and quantum yield of the process. The efficiency of these photoinitiators was discussed on the basis of the free energy change for electron transfer from a borate anion to an excited hemicyanine dye cation. The ∆Gel values were estimated for photoredox pairs containing a series of phenyltrialkylborate anions and one styrylpyridinium dye cation. The relationship between the rate of polymerization and the free energy of activation for electron transfer reaction gives the dependence predicted by the classical theory of electron transfer. The photoinitiating abilities of the selected novel photoredox pairs (BPB61, BPB7, BPB8, and BPB9) are comparable with the photoinitiating efficiency of commercially available photoinitiators.


Residency Program Use of Social Media in the COVID-19 Era: An Applicant's Perspective.
General surgery residency programs' use of social media has exploded since early spring 2020, as it became clear that the COVID-19 pandemic would prevent away rotations and in-person interviews. Faced with the prospect of ranking programs they cannot visit, applicants are becoming reliant on programs' use of social media to showcase program culture, now a key recruitment tool. However, proper etiquette for applicant engagement with programs' social media accounts is unclear. Who administers these accounts - residents, program directors, program coordinators, or marketing staff? The subjectivity of criteria for "potentially unprofessional" content may pose disproportionate risks to female applicants and applicants of color. From this applicant's perspective, programs' recent use of social media has been informative and humanizing. It is our hope that departments, programs, and residents continue to post on social media throughout the application cycle. However, we applicants would benefit from clear guidance and expectations as to how to engage with residency programs via social media.


Biceps tenodesis: a biomechanical study of fixation methods.
Rupture of the biceps tendon occurs predominantly in the middle-aged and elderly, being predisposed through bicipital tendinitis and rotator cuff lesions. Surgical repair may be an option for those requiring strength in supination. This study compared the initial fixation strength of keyhole tenodesis (n = 7) and interference screw fixation by use of cadaveric specimens. Two interference screws were evaluated (n = 7 x 2): the round-headed cannulated interference screw (RCI) and a bioresorbable screw (Sysorb). All specimens failed at the fixation site but one. This study found that overall there was a significant effect as a result of study group (keyhole vs Sysorb vs RCI, P =.034). The post hoc comparisons revealed that the keyhole was significantly stronger than the RCI screw (P =.033) but not significantly different compared with the Sysorb screw (P =.129). No significant difference was observed between the Sysorb and RCI screws (P =.762). Interference screw fixation failed by tendon slippage at the screw-tendon-bone interface; keyhole fixation failed by tendon splitting and slippage out of the restraining keyhole. Keyhole tenodesis may permit earlier postoperative mobilization when compared with tenodesis by use of interference screw fixation.


Indeterminate calcification and clustered cystic lesions are strongly predictive of the presence of mucocele-like tumor of the breast: a report of six cases.
Mucocele-like tumor (MLT) of the breast is a mucinous disorder that is generally difficult to distinguish from mucinous carcinoma. Moreover, MLT is often accompanied by atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), and preoperative diagnosis is very confusing. In this paper, we summarize the clinicopathological characteristics of six cases of MLTs, comparing them with mucinous carcinoma. MLTs were characterized by clustered, coarse calcification on mammography and clustered, hypoechoic lesions with or without echogenic spots on ultrasonography. On fine-needle aspiration cytology (FNAC), three cases were correctly diagnosed and three cases were judged to be indeterminate, or insufficient material was present. Ultimately, excisional biopsies were performed to obtain a correct diagnosis in all cases. Immunohistochemical staining of MLTs accompanied by ADH or DCIS (malignant MLTs) revealed the presence of MUC6, while MLTs without ADH or DCIS (benign MLTs) were MUC6-negative. At present, as it is difficult to detect small areas of DCIS adjacent to the MLT by FNAC, excisional biopsy is essential. Immunohistochemical staining for MUC6 may be useful in differentiating between benign MLTs and malignant MLTs, although further investigation is needed.


To avoid post-operative refractive error in cataract surgery.
One of the greatest issues facing the cataract surgeon today is accurate prediction of post-operative refractive error. With use of intraoperative autorefractometry (IOAR), such errors can be detected and post-operative refractive errors avoided. An 83-year-old woman was admitted for right eye phacoemulsification, with aimed at -1.78D with Sanders/Retzlaff/Kraff/T (SRK/T) formula implantation under local anesthesia. IOAR was performed after IOL insertion. The first estimate was +1.1D, indicating hyperopia, and far from the desired refraction above 2D. IOL exchange to +11.5D was, therefore, performed. The second estimate was -0.13D and the operation was completed. The final refraction (3 years after operation) was -0.25D. With IOAR, we were able to avoid the unpleasant surprise of a mistaken intraocular lens power. Intraoperative autorefractometry is useful for avoiding errors in IOL power.


Salivary alpha-amylase response following repeated psychosocial stress in patients with panic disorder.
This study examined autonomic responses (salivary alpha-amylase, sAA; heart rate, HR) to repeated psychosocial stress as a candidate mechanism linking autonomic hyper-arousal and sensitization to the occurrence of panic disorder (PD). Thirty-three patients with PD and 34 healthy controls were exposed to the Trier Social Stress Test (TSST) twice on consecutive days. sAA changes were comparable between PD and controls on both testing days with overall decreasing sAA responses (delta) on day two. In contrast, HR delta increased on day two in both groups. This sensitization was driven by female controls while male PD showed most pronounced HR changes to the first TSST. Overall, a general autonomic hyper-arousal in PD could not be confirmed. In contrast, sAA responses slightly habituated to repeated stress. Whether sAA findings mirror assumed habituation effects of repeated stress exposure on normalizing autonomic reactivity remains to be investigated in longitudinal studies.


Tertiary resurfacing after one of the first free flaps in Europe, a reflection on 30 years of microsurgical progress.
Free flaps have been used for over 30 years. During this period, improved anatomical understanding has increased donor options and available pedicle lengths, permitting safer, single-stage reconstructions with simpler anastomoses. Refinements, such as perforator flaps in particular, have greatly improved donor morbidity, recipient site cosmesis, and the ability to replace 'like with like' while retaining options for innervation. This case highlights the evolution from one of Europe's first free tissue transfers, effectively a perforator flap, through the advent of free muscle flaps to the current generation of contourable perforator flaps. Free flap transfer has become increasingly sophisticated, safer, and more predictable, yet the potential quality of reconstructive outcome has changed little.


Novel 'inflammatory plaque' pathology in presenilin-1 Alzheimer's disease.
Inflammation, in the form of reactive astrocytes and microglia, is thought to play an important role in Alzheimer's disease (AD) pathogenesis where it correlates with brain atrophy and disease severity. The Abeta protein, which comprises senile plaques, is thought to be responsible for initiating this inflammatory response. Despite having a more aggressive disease process and greater Abeta deposition, few studies have investigated inflammation in early onset AD cases with mutations in the presenilin-1 (PS-1) gene. In fact, many researchers place importance on a variant plaque pathology in PS-1 cases, known as cotton wool plaques, which lack significant inflammatory infiltrate. We investigated the association between inflammation and plaque pathology in PS-1 AD. Classic cored, cotton wool and diffuse Abeta plaques were observed in all cases. PS-1 cases also exhibited a novel plaque pathology with a significantly greater inflammatory response in the form of reactive microglia and astrocytes. These 'inflammatory plaques' consisted of a dense cresyl violet-, silver-, and thioflavin S-positive, but Abeta-, tau-, apolipoprotein E (ApoE)-, non-Abeta component of Alzheimer's disease amyloid (NAC)- and PS-1-negative core. These findings indicate potent stimulator(s) of inflammation that are not typical of the Abeta that accumulates in the pathological hallmarks of sporadic AD. Identification of this substance may be important for the development of future therapeutic strategies.


Nuclear pore ion channel activity in live syncytial nuclei.
Nuclear pore complexes (NPCs) are important nanochannels for the control of gene activity and expression. Most of our knowledge of NPC function has been derived from isolated nuclei and permeabilized cells in cell lysates/extracts. Since recent patch-clamp work has challenged the dogma that NPCs are freely permeable to small particles, a preparation of isolated living nuclei in their native liquid environment was sought and found: the syncytial nuclei in the water of the coconut Cocos nucifera. These nuclei have all properties of NPC-mediated macromolecular transport (MMT) and express foreign green fluorescent protein (GFP) plasmids. They display chromatin movement, are created by particle aggregation or by division, can grow by throwing filaments to catch material, etc. This study shows, for the first time, that living NPCs engaged in MMT do not transport physiological ions - a phenomenon that explains observations of nucleocytoplasmic ion gradients. Since coconuts are inexpensive (less than US$1/nut per litre), this robust preparation may contribute to our understanding of NPCs and cell nucleus and to the development of biotechnologies for the production of DNA, RNA and proteins.


Development and Regulation of Connected Combined Products: Reflections From the Medtech & Pharma Platform Association.
Patients taking a medicinal product in a homecare setting typically use a medical device to facilitate the injection process. Reductions in wireless connectivity costs, combined with the rapid adoption of smartphones with connectivity to cloud-based services, are enabling these drug delivery devices to now be connected to a digital ecosystem as connected combined products (CCPs). The purposes of this article are to identify the challenges in developing and releasing these products when they straddle different regulatory frameworks and standards and to highlight gaps in the European Union regulations. Industry subject matter experts from pharmaceutical, medical device, and consultancy companies, who are members of the Medtech & Pharma Platform Association, formed 4 working groups to address current best practice for developing and releasing CCPs and the different relevant regulatory frameworks. The 4 areas studied were clinical and regulatory, usability and human factors engineering, development and life cycle management, and cybersecurity. Development teams require new skills to create innovative products that have a good safety profile and are simple to use, such as design thinking to understand user needs and systems engineering to manage complexity and ensure interoperability. Risk management process should integrate cybersecurity, data privacy, and data integrity, whereas design control processes should enable asynchronous development cycles for hardware and software components. Regulatory frameworks exist for individual components within the CCP. However, for a complex product, regulatory guidance is needed when combining components with different risk and safety profiles and to ensure that the responsibilities and liabilities of companies contributing components are clear. The efficient management of software changes and product updates, as well as dealing with end-of-life hardware and backward compatibility to older software versions, needs agile approaches when it comes to regulatory updates. The regulatory uncertainties and development processes outlined in this article need to be addressed. We call for joint discussions among the various stakeholders in the fields of medicinal products, medical devices, and in vitro diagnostics, as well as standalone software, data protection, and cybersecurity experts, together with regulators and lawmakers in the European Union to meet in focused discussion groups with the aim of devising pragmatic solutions and regulations for the benefit of the sector and hence the patients it serves.


Accessory blood supply to the liver from the dorsal pancreatic artery: an unusual anatomic variant.
A case of an accessory hepatic artery from the dorsal pancreatic artery is illustrated. A discussion of anatomic variations and embryology of the arterial blood supply to the liver from the celiac axis and aberrant blood supply from other vessels is presented with a consideration of the surgical and diagnostic significance of anatomic variance.


Recent advances in the treatment of GERD in the elderly: focus on proton pump inhibitors.
The prevalence of gastroesophageal reflux disease (GERD) increases with age, and older people are more likely to develop severe disease. Studies of elderly patients with GERD indicate differences in presentation and diagnosis, compared with GERD in younger adults. Indeed, an older patient with GERD may present with atypical symptoms such as dysphagia, vomiting, weight loss, anaemia and anorexia, and less frequently with typical symptoms such as heartburn or acid regurgitation. These findings are attributed to pathophysiological changes in esophageal function that occur with age. Therefore, GERD in elderly patients is more likely to be poorly diagnosed or undiagnosed. Although few studies have concentrated specifically on elderly patients, the proton pump inhibitors (PPIs) have been shown to be more effective than histamine receptor antagonists for healing reflux esophagitis and for preventing its recurrence when they are given as maintenance therapy. In addition, the PPIs seem to be safe both in short- and in long-term therapy of elderly patients with GERD.


Differential Quercus spp. pollen-particulate matter interaction is dependent on geographical areas.
Particulate matter (PM) and pollen interaction, either airborne or at the respiratory mucosa needs further clarification, as allergic reaction intensification can be related to the PM physical characteristics and toxicity. This study aimed to investigate the physical-chemical properties of PM that can adhere to the pollen wall during its transport or inhalation, using Quercus spp. as a model, in three Portuguese cities with different geographical locations, meteorological influence and urbanization levels. Possible sources were evaluated through air masses trajectory analysis using the HYSPLIT model and correlation with meteorological factors. The sampling was performed using a 7-days Hirst-type volumetric sampler, and the pollen grains were observed using a Field Emission Electron Probe Microanalyser for PM analysis. A secondary electron image of each pollen grain was taken, to determine the adhered particles characteristics and energy dispersive x-ray spectroscopy (EDS) spectra were obtained for individual particles. A total of 484 pollen grains was observed, with 7683 particles counted and 1914 EDS spectra analyzed. The particle's equivalent diameter ranged from 0.3-16 μm, with most having a diameter < 3 μm. For the three cities, there were significant differences in the number of particles per pollen and the % area occupied by the particles. Particles adhered were mainly Si-rich, but variations in other dominant groups were observed. For Évora and Guarda, Ca-rich, SO-rich were second and third more representative, while Porto were Organic and Cl-rich. Metals&Oxides were found in all cities with the highest number in Porto. P-rich particles were only found in Évora. Sea salt particles were observed in Évora, coincide with air mass trajectories possible carrying them from the Mediterranean Sea. In conclusion, the PM physical characteristics are similar between the studied cities, however, the dominant chemical composition is different, certainly impacting the exposome influence and pollen-allergy intensification towards the same pollen type and concentration.


Comparative activities of novel beta-lactamase inhibitors, 6-exomethylene penamsulfones (CH1240, CH2140) in experimental mouse infection model.
The antibacterial activity of novel beta-lactamase inhibitors, 6-exomethylene penamsulfones (CH1240, CH2140), has been compared in vivo with that of sulbactam and clavulanic acid against beta-lactamase producing strains. In vivo microbiological assessment was used as experimental mouse infection model by gram negative strains. Against Pseudomonas aeruginosa F0013, cefoperazone/CH1240 was slightly less active than sulbactam. Ampicillin/CH1240 was more active than sulbactam against Citrobacter diversus species. That of ampicillin/CH2140 was less effective than sulbactam against Escheriachia coli 3457. Especially against Citrobacter diversus 2046E, amoxicillin/CH2140 was the most potent and amoxicillin/CH1240 was slightly more active than clavulanic acid. Consequently the difference in efficacy between the drug combinations appears to be related to the degree of protection afforded the animals by the beta-lactamase inhibitors. CH1240 and CH2140 are promising new agents and should undergo further investigations.


Crohn's disease: "its gynecologic aspect".
An analysis of the medical records of 103 women with Crohn's disease points up the following observations. There is a slight increase in spontaneous abortions and a substantial degree of subfertility. The obstetric experience is the same as in the normal obstetric population and the effects of the disease on pregnancy and of pregnancy on the disease are minimal. Features seemingly unrelated to Crohn's disease and of a gynecologic nature may be present months before the onset of the main bowel inflammation. These features consist of abscesses, fistulas, ulcers, fissures, and infections involving not only the internal pelvic organs but also the vulvovagina, perineum, labia, rectovaginal septum, rectum, and anus. The onset of Crohn's disease may be acute and present the picture of an abdomen requiring surgical treatment. A tender, low abdominal, adnexal, or pelvic mass may incorrectly be diagnosed as acute appendicitis, pelvic inflammatory disease, or ovarian cyst, and lead to surgery. In 23 instances the diagnosis of Crohn's disease was established only after laparotomy. A total of 27 appendectomies were performed and none of these patients had acute appendicitis. Four pelvic abscesses developed after the appendectomies. To avoid the pitfalls of misdiagnosis and mismanagement, the nature of Crohn's disease should be understood and the gynecologic aspects of the disease recognized.


Pre-equilibrium biosensors as an approach towards rapid and continuous molecular measurements.
Almost all biosensors that use ligand-receptor binding operate under equilibrium conditions. However, at low ligand concentrations, the equilibration with the receptor (e.g., antibodies and aptamers) becomes slow and thus equilibrium-based biosensors are inherently limited in making measurements that are both rapid and sensitive. In this work, we provide a theoretical foundation for a method through which biosensors can quantitatively measure ligand concentration before reaching equilibrium. Rather than only measuring receptor binding at a single time-point, the pre-equilibrium approach leverages the receptor's kinetic response to instantaneously quantify the changing ligand concentration. Importantly, by analyzing the biosensor output in frequency domain, rather than in the time domain, we show the degree to which noise in the biosensor affects the accuracy of the pre-equilibrium approach. Through this analysis, we provide the conditions under which the signal-to-noise ratio of the biosensor can be maximized for a given target concentration range and rate of change. As a model, we apply our theoretical analysis to continuous insulin measurement and show that with a properly selected antibody, the pre-equilibrium approach could make the continuous tracking of physiological insulin fluctuations possible.


A new experimental animal for the study of age-related changes in serotonergic neuronal activity in the brain cortex.
Calcium uptake by the cortical synaptosomes in a rodent (Fischer rat) and an insectivore shrew (Suncus murinus) was detected as a parameter reflecting molecular dysfunction of the aging brain. The change in calcium uptake by the cortical synaptosomes in both species was concomitant which showed less than half the capacity at 24 months old animals compared with those at 8 months old. On the other hand, 5-hydroxytryptamine binding and imipramine binding to the membrane fraction of aging rat brain cortex was not altered in terms of binding capacity along with aging, while, in Suncus, the binding of both serotonergic ligands declined with aging. In order to elucidate decreased serotonergic activity in human demented aged brain, together with declining activity in neurotransmitting systems detectable as a function of calcium uptake by the cortical synaptosomes, Suncus may be an appropriate animal model for studying physiological aging processes in the mammalian brain cortex.


Relation between electromyogram and torque of isometric reflex contractions in man.
Human subjects maintained isometric plantar or dorsal flexions of the ankle in a matching task. H-reflexes of different sizes were superimposed on the steady activity. The peak-to-peak amplitude of the reflexes was measured on the electromyogram (EMG) of the soleus muscle. The size of the corresponding muscle contractions was determined on the isometric torque signal in relation to the maintained flexion force. The EMG-torque relation which was defined as the reflex muscle contraction as a function of the EMG reflex signal approximated a square root function for a given steady contraction level. It was not modulated by steady dorsal flexions, but it decreased continuously with stronger plantar steady torques. This dependence was caused by the silent period following the reflex discharge. Since the reflex discharge and the silent period were near in time to the duration of the contraction, the silent period had a direct effect on the reflex contraction amplitude.


Coronary Artery Anomalies Are Associated With Increased Mortality After Truncus Arteriosus Repair.
Truncus arteriosus is associated with coronary anomalies. We identified coronary artery lesions in patients undergoing repair of truncus arteriosus, defined the impact of lesions on mortality, and studied the effect of surgical intervention of coronary lesions. A retrospective review identified 107 patients with truncus repair (1995-2019). Coronary lesions were categorized as ostial stenosis, intramural, juxtacommissural origin, and single coronary. Survival analysis characterized survival after truncus repair and studied the association of coronary lesions and mortality. Among 107 patients with truncus repair 34 patients had at least 1 coronary lesion. Median follow-up time was 7 years, with 85% 5-year survival. Coronary lesions including ostial stenosis, intramurality, and juxtacommissural origin were associated with increased mortality, whereas single coronaries did not impact survival. Eleven patients had 1 coronary lesion and 6 patients with 2 coronary lesions had similar (80% and 83%, respectively) 5-year survival. Eight patients with 3 coronary lesions had 24% 5-year survival (P = .0003). Among patients with 1 or 2 lesions, surgical intervention on the coronary lesions tended to be associated with longer 5-year survival (100% vs 62%, respectively; P = .06). All patients with 3 lesions underwent coronary artery intervention, with 24% 5-year survival. Impact of coronary lesions on mortality after truncus repair increases with the number of lesions. Coronary artery intervention may be associated with improved time-related survival among patients with 1 or 2 lesions. Patients with the most complex anomalies (3 lesions) have poor survival and warrant ongoing study of repair techniques.


ExTRACT-TIMI 25 in perspective: key lessons regarding enoxaparin as an adjunct to fibrinolytic therapy.
Unfractionated heparin (UFH) for 48 h has been the traditional standard anticoagulant with fibrinolytics. The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction (ExTRACT)-Thrombolysis in Myocardial Infarction (TIMI) 25 trial prospectively studied the usefulness of enoxaparin and found that in patients treated with fibrinolysis, enoxaparin administered throughout the index hospitalization was superior to the standard 48-h UFH infusion. However, enoxaparin increased major bleeding. The data from this large trial were further analyzed across various subgroups and these results support the use of enoxaparin in a broad range of patients. The ExTRACT-TIMI 25 trial employed a novel dosing regimen for enoxaparin adjusted for age and renal function, which was designed to minimize bleeding risk while maintaining the beneficial effects of enoxaparin. Based on the evidence from this trial, the 2007 ST-segment elevation myocardial infarction guidelines now preferentially recommend enoxaparin to be administered throughout the index hospitalization as per the dosing regimen used in ExTRACT-TIMI 25 in most patients treated with fibrinolytic therapy.


Revisiting detachment techniques in human-biting ticks.
Early and complete removal of ticks using the right technique is important to reduce tick-transmitted diseases. Several chemical and mechanical detachment techniques have been described previously. We aimed to compare the performance of 4 tick-detachment techniques that are widely used in human beings and to determine the optimal method from these techniques. A cross-sectional study was conducted on 160 patients between April and June 2010. Patients with reported tick bite were reviewed retrospectively and divided into the following 4 groups according to the tick-detachment technique used: card detachment, lassoing, freezing, and tweezers. Performance of each technique was evaluated according to the number of fully detached, nondetached, and crushed ticks and the duration of application. Of the 160 tick-bite cases assessed, we found the following efficacy rates: 82.5% (33/40), technique using tweezers; 47.5% (19/40), lassoing technique; 7.5% (3/40), card detachment; and 0% (0/40), freezing technique. The efficacy rate of the technique using tweezers was significantly higher than that of the other 3 techniques (P < .05). This was a relatively small sample size and not designed as a randomized clinical trial. Tick detachment using tweezers, performed in an appropriate manner, is the easiest and most effective technique.


A qualitative study of stakeholder views of the conditions for and outcomes of successful clinical networks.
Clinical networks have been established to improve health outcomes and processes of care by implementing a range of innovations and undertaking projects based on perceived local need. Limited research exists on the necessary conditions required to bring about successful network outcomes and what characterises network success from the perspective of those involved in network initiatives. This qualitative study identified stakeholder views on i) the conditions for effective clinical networks; and ii) desirable outcomes of successful clinical networks. Twenty-seven participants were interviewed using face-to-face audio-recorded semi-structured interviews. Transcribed data were coded and analysed to generate themes relating to the study aims. Five key factors represented as sub-themes were identified as important conditions for the establishment of successful clinical networks under the main theme of effective network structure, organisation and governance. These were: building relationships; effective leadership; strategic evidence-based workplans; adequate resources; and ability to implement and evaluate network initiatives. Two major themes encapsulated views on desirable outcomes of successful clinical networks: connecting and engaging which represented the outcomes of interdisciplinary and consumer collaboration and, partnerships with state health and local health services, and changing the landscape of care, which represented the importance of outcomes associated with improving services, care and patient health outcomes and implementing evidence-based practice. This study provides new knowledge on the conditions needed to establish successful clinical networks and on desirable outcomes arising from network projects and initiatives that are considered to be valuable by those working in or associated with clinical networks. This provides health services with information on what needs to be in place for successful networks and on the types of outcomes that can be considered for assessing network effectiveness.


Anaerobes in Industrial- and Environmental Biotechnology.
Anaerobic microorganisms present in diverse ecological niches employ alternative strategies for energy conservation in the absence of oxygen which enables them to play a key role in maintaining the global cycles of carbon, nitrogen, and sulfur, and the breakdown of persistent compounds. Thereby they become useful tools in industrial and environmental biotechnology. Although anaerobes have been relatively neglected in comparison to their aerobic counterparts, with increasing knowledge about their diversity and metabolic potential and the development of genetic tools and process technologies to utilize them, we now see a rapid expansion of their applications in the society. This chapter summarizes some of the developments in the use of anaerobes as tools for biomass valorization, in production of energy carriers and chemicals, wastewater treatment, and the strong potential in soil remediation. The ability of several autotrophic anaerobes to reduce carbon dioxide is attracting growing attention as a means for developing a platform for conversion of waste gases to chemicals, materials, and biofuels.


Modification of the binding of sulphamidochlorobenzoic acid to human albumin by palmitic acid contamination of albumin.
Palmitic acid a common contaminant of albumin preparations, competitively inhibits the binding of sulphamidochlorobenzoicacid (SCBA) to human albumin thus decreasing its observed affinity. The effect of palmitic acid depends on its concentration, i.e. the purity and concentration of the albumin preparation used. The correct value for SCBA affinity was obtained by correcting the experimental data according to the palmitic acid concentration by use of a multiligand analysis method.


A DPOAE assessment of outer hair cell integrity in ears with age-related hearing loss.
Distortion product otoacoustic emissions (DPOAEs) were used to assess outer hair cell (OHC) integrity in human ears with age-related hearing loss. Sound pressure measurements were made in the ear canal over the stimulus range 40-90 dB SPL (L2), with L1 = 0.45*L2 + 44 with F2 = 2 and 3 or 4 kHz. Model-generated DPOAE I/O functions were fit to DPOAE data to quantify the contribution of loss of nonlinearity (OHC loss) to the hearing loss. Results suggest OHC loss as a contributing cause of age-related hearing, regardless of audiogram configuration. It seems likely that OHC and strial pathology co-exist in ears with AHL.


Life-history strategies of a freshwater snail in response to stream permanence and predation: balancing conflicting demands.
Life-history parameters for the freshwater snail Physella virgata virgata were estimated in temporary and permanent streams with and without crayfish (known snail predators). Snails from the permanent stream with crayfish exhibited higher age and size at first reproduction, as well as higher size and age at death, compared to snail populations from both temporary streams and the permanent stream without crayfish. Life-history patterns of snails from the permanent and temporary streams without crayfish were indistinguishable, with small sizes at first reproduction and at death, as well as lower age at first reproduction and at death. The snail population from the temporary stream with crayfish showed an intermediate life-history pattern. The results suggest that snail life-history patterns vary with both predation pressure and habitat stability, exhibiting phenotypically plastic responses to the variables.


Effective genome editing and identification of a regiospecific gallic acid 4-O-glycosyltransferase in pomegranate (Punica granatum L.).
Pomegranate (Punica granatum L.) trees are woody perennials that bear colorful and nutritious fruits rich in phenolic metabolites, e.g., hydrolyzable tannins (HTs) and flavonoids. We here report genome editing and gene discovery in pomegranate hairy roots using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9), coupled with transcriptome and biochemical analyses. Single guide RNAs (sgRNAs) were designed to target two UDP-dependent glycosyltransferases (UGTs), PgUGT84A23 and PgUGT84A24, which possess overlapping activities in β-glucogallin (a galloylglucose ester; biosynthetic precursor of HTs) biosynthesis. A unique accumulation of gallic acid 3-O- and 4-O-glucosides (galloylglucose ethers) was observed in the PgUGT84A23 and PgUGT84A24 dual CRISPR/Cas9-edited lines (i.e., ugt84a23 ugt84a24) but not the control (empty vector) or PgUGT84A23/PgUGT84A24 single edited lines (ugt84a23 or ugt84a24). Transcriptome and real-time qPCR analyses identified 11 UGTs with increased expression in the ugt84a23 ugt84a24 hairy roots compared to the controls. Of the 11 candidate UGTs, only PgUGT72BD1 used gallic acid as substrate and produced a regiospecific product gallic acid 4-O-glucoside. This work demonstrates that the CRISPR/Cas9 method can facilitate functional genomics studies in pomegranate and shows promise for capitalizing on the metabolic potential of pomegranate for germplasm improvement.


Nodal metastases of nasopharyngeal carcinoma: patterns of disease on MRI and FDG PET.
The patterns of nodal spread of nasopharyngeal carcinoma (NPC) have an important influence on treatment planning, but have not yet been fully addressed. We prospectively used MRI and FDG PET to document the patterns of nodal spread in NPC. One hundred and one patients with newly diagnosed NPC were studied with MRI and FDG PET. On MRI, nodes were considered as metastatic according to criteria regarding size, the presence of nodal necrosis, and extracapsular spread. FDG PET images were interpreted visually, and nodes were considered metastatic if they showed prominent FDG uptake against the background. Nodal metastases were found in 89 of our 101 patients. Analysis of the distributions of nodal metastases in these 89 patients showed that retropharyngeal nodes were less frequently involved than cervical nodes (82.0% vs 95.5%). The vast majority of cervical nodal metastases were to the internal jugular chain, including nodes at levels II, III, and IV, with decreasing incidences of 95.5%, 60.7%, and 34.8%, respectively. Level V nodal involvement was found in 27% of patients. Supraclavicular fossa nodal metastases were not uncommon and occurred in 22.5% of patients. Skip metastases in the lower-level nodes or supraclavicular fossa nodes occurred in 7.9% of patients. Mediastinal and abdominal metastatic adenopathy was present in 4.5% and 3.4% of patients, respectively, and was associated with advanced nodal metastasis in the supraclavicular fossa. Level VI (2.2%), level VII (1.1%), submandibular (2.2%), and parotid (3.4%) nodal metastases were uncommon and were always associated with advanced ipsilateral nodal metastases of the neck. We conclude that the combined use of FDG PET and MRI can comprehensively depict the pattern of nodal metastasis in NPC patients. Nodal metastases principally affected level II nodes, from which lymphatic spread extended down in an orderly manner to involve level III, level IV, and the supraclavicular fossa nodes, or extended posteriorly to involve level V nodes. The frequency of skip metastases was 7.9%. Distant spread to mediastinal or abdominal nodes was found in 3-5% of patients, usually in association with supraclavicular nodal metastases.


Rapidly progressive soft tissue infections.
Skin and soft tissue infections are among the most common reasons for people to seek medical advice. They also represent one of the most common indications for antimicrobial therapy and account for approximately 7-10% of hospitalisations in North America. Although non-limb and non-life threatening infections may be treated on an out-patient basis with oral antibiotics, patients with more serious acute skin and soft tissue infections may require admission to hospital for management; this decision is especially true if the infection is rapidly progressive. We provide a concise overview of the differential diagnosis and approach to management of community-acquired rapidly progressive skin and soft tissue infections.


[Analysis of palliative sedation in hospitalised elderly patients: Effectiveness of a protocol].
To measure changes in the practice of palliative sedation during agony in hospitalised elderly patients before and after the implementation of a palliative sedation protocol. A retrospective before-after study was performed in hospitalised patients over 65 years old who received midazolam during hospital admission and died in the hospital in two 3-month periods, before and after the implementation of the protocol. Non-sedative uses of midazolam and patients in intensive care were excluded. Patient and admission characteristics, the consent process, withdrawal of life-sustaining treatments, and the sedation process (refractory symptom treated, drug doses, assessment and use of other drugs) were recorded. Association was analysed using the Chi(2) and Student t tests. A total of 143 patients were included, with no significant differences between groups in demographic characteristics or symptoms. Do not resuscitate (DNR) orders were recorded in approximately 70% of the subjects of each group, and informed consent for sedation was recorded in 91% before vs. 84% after the protocol. Induction and maintenance doses of midazolam followed protocol recommendations in 1.3% before vs 10.4% after the protocol was implemented (P=.02) and adequate rescue doses were used in 1.3% vs 11.9% respectively (P=.01). Midazolam doses were significantly lower (9.86mg vs 18.67mg, P<.001) when the protocol was used than when it was not used. Ramsay sedation score was used in 8% vs. 12% and the Palliative Care Team was involved in 35.5% and 16.4% of the cases (P=.008) before and after the protocol, respectively. Use of midazolam slightly improved after the implementation of a hospital protocol on palliative sedation. The percentage of adequate sedations and the general process of sedation were mostly unchanged by the protocol. More education and further assessment is needed to gauge the effect of these measures in the future.


The Emergency Department Longitudinal Integrated Care (ED-LINC) intervention targeting opioid use disorder: A pilot randomized clinical trial.
Opioid use disorder (OUD) and related comorbid conditions are highly prevalent among patients presenting to emergency department (ED) settings. Research has developed few comprehensive disease management strategies for at-risk patients presenting to the ED that both decrease illicit opioid use and improve initiation and retention in medication treatment for OUD (MOUD). The research team conducted a pilot pragmatic clinical trial that randomized 40 patients presenting to a single ED to a collaborative care intervention (n = 20) versus usual care control (n = 20) conditions. Interviewers blinded to patient intervention and control group status followed-up with participants at 1, 3, and 6 months after presentation to the ED. The 3-month Emergency Department Longitudinal Integrated Care (ED-LINC) collaborative care intervention for patients at risk for OUD included: 1) a Brief Negotiated Interview at bedside, 2) overdose education and facilitation of MOUD, 3) longitudinal proactive care management, 4) utilization of the statewide health information exchange platform for 24/7 tracking of recurrent ED utilization, and 5) weekly caseload supervision that incorporated measurement-based care treatment assessment with stepped-up care for patients with recalcitrant symptoms. Overall, the ED-LINC intervention was feasibly delivered and acceptable to patients. The pilot study achieved >80% follow-up rates at 1, 3, and 6 months. In adjusted longitudinal mixed model regression analyses, no statistically significant differences existed in days of opioid use over the past 30 days for ED-LINC intervention patients when compared to patients receiving usual care (incidence-rate ratio (IRR) 1.50, 95% CI 0.54-4.16). The unadjusted mean number of days of illicit opioid use decreased at the 1-month and 3-month follow-up time points for both groups. ED-LINC intervention patients had increased rates of MOUD initiation compared to control patients (50% versus 30%); intervention versus control comparisons did not achieve statistical significance, although power to detect significant differences in the pilot was limited. The ED-LINC intervention for patients with OUD can be feasibly implemented and warrants testing in larger scale, adequately powered randomized pragmatic clinical trial investigations. gov NCT03699085.


Coat color affects the resilience against heat stress impacts on testicular hemodynamics, reproductive hormones, and semen quality in Baladi goats.
Drastic climatic changes threaten animal productivity and prolificacy, whose adaptability is governed by its pheno- and genotypic traits. This study was aimed at investigating the effect of coat color on the adaptability of goat bucks under heat stress conditions from the perspectives of testicular blood flow (TBF) and biometry, reproductive hormones, and semen quality. Twenty bucks (Capra hircus) bearing different coat colors were selected from a large flock and divided into four equal groups (n = 5 each) as follows: black coat (BC; 100% black), brown coat (BrC; 100% dark brown), white coat (WC; 100% white), white-black coat (WBC; 50-60% white). Bucks were examined for TBF [Doppler ultrasonography and serum nitric oxide (NO)], testosterone (T) and luteinizing hormone (LH), seminal plasma oxidative biomarkers [catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA)], and sperm traits percentages [progressive motility (PM), viability (SV), normal morphology (NM), and sperm concentration (SC) once a week for seven consecutive weeks (W1-W7) in the summer season (temperature humidity index = 88.4-92.2). Specifically, at W3-W7, darker bucks (BC and BrC) testicular volume, testicular colored area, T, NO, CAT, TAC, PM, SV, NM, and SC (W7 only) differed significantly (P < 0.05) by decrease than the lighter ones (WC and WBC). Both Doppler indices and serum MDA concentrations were elevated (P < 0.05) at W3-W7 in the BC and BrC bucks compared to WC and WBC groups. In conclusion, bucks with lighter coats were more resistant to the negative effects of HS on TBF, seminal oxidative biomarkers, and semen quality.


Alternative operative procedure for total colonic aganglionosis.
The authors have utilized a technique recently described by Boley as the corrective procedure in two patients with complex long segment aganglionosis. The one-stage operation combines a right colon onlay patch for enhanced absorptive and reservoir purposes with an ileoendorectal pull-through. Both patients had only 3 to 4 stools per day by the end of the first postoperative month. The obligatory period of intestinal adaptation needed to achieve an acceptable stooling pattern is significantly reduced in comparison with results obtained with other commonly used procedures.


Voluntary exercise ameliorates synaptic pruning deficits in sleep-deprived adolescent mice.
Adolescence is a critical period for brain development and adequate sleep during this period is essential for physical function and mental health. Emerging evidence has detailed the neurological impacts of sleep insufficiency on adolescents, as was unveiled by our previous study, microglia, one of the crucial contributors to synaptic pruning, is functionally disrupted by lack of sleep. Here, we provided evidence featuring the protective effect and the underlying mechanisms of voluntary exercise (VE) on microglial functions in an adolescent 72 h sleep deprivation (SD) model. We identified that the aberrant hippocampal neuronal activity and impaired short-term memory performance in sleep-deprived mice were prevented by 11 days of VE. VE significantly normalized the SD-induced dendritic spine increment and maintained the microglial phagocytic ability in sleep-deprived mice. Moreover, we found that the amendment of the noradrenergic signal in the central nervous system may explain the preventative effects of VE on the abnormalities of microglial and neuronal functions caused by SD. These data suggested that VE may confer protection to the microglia-mediated synaptic pruning in the sleep-deprived adolescent brains. Therefore, physical exercise could be a beneficial health practice for the adolescents that copes the adverse influence of inevitable sleep insufficiency.


Multi-class methodology to determine pesticides and mycotoxins in green tea and royal jelly supplements by liquid chromatography coupled to Orbitrap high resolution mass spectrometry.
A multi-class methodology was developed to determine pesticides and mycotoxins in food supplements. The extraction was performed using acetonitrile acidified with formic acid (1%, v/v). Different clean-up sorbents were tested, and the best results were obtained using C18 and zirconium oxide for green tea and royal jelly, respectively. The compounds were determined using ultra high performance liquid chromatography (UHPLC) coupled to Exactive-Orbitrap high resolution mass spectrometry (HRMS). The recovery rates obtained were between 70% and 120% for most of the compounds studied with a relative standard deviation <25%, at three different concentration levels. The calculated limits of quantification (LOQ) were <10 μg/kg. The method was applied to green tea (10) and royal jelly (8) samples. Nine (eight of green tea and one of royal jelly) samples were found to be positive for pesticides at concentrations ranging from 10.6 (cinosulfuron) to 47.9 μg/kg (paclobutrazol). The aflatoxin B1 (5.4 μg/kg) was also found in one of the green tea samples.