A scanning electron microscopy study of the interface between ceramics and bone.
By use of scanning electron microscopy (SEM), together with energy dispersive chemical analysis, a study has been made of the comparison of an in vitro method of assessing interface reactions between bone and ceramic implants with the naturally occurring changes seen in the rat ear model. Interface reactions between bone and two ceramic materials were examined following 4 wk in culture and 4 wk implantation. In both cases a gradual chemical change occurred at the calcium silicate surface during the fibrous growth onto the ceramic material. Gradual mineralization of the connective fibres was found at the interface of the calcium silicate material, whereas, in the case of alumina ceramic a connective fibrous bond had formed with no associated chemical change at the ceramic surface.


Global health education for medical students in Italy.
Global health education (GHE) in Italy has spread since the first decade of 21st century. The presence of global health (GH) courses in Italy was monitored from 2007 to 2013. In 2019, a new survey was proposed to assess the availability of educational opportunities in Italian medical schools. An online survey was carried out using a questionnaire administered to a network of interested individuals with different roles in the academic world: students, professors, and members of the Italian Network for Global Health Education. The features of courses were analysed through a score. A total of 61 responses were received from affiliates of 33 out of the 44 medical schools in Italy. The national mean of GH courses for each faculty was 1.2, reflecting an increase from 2007. The courses increased nationwide, resulting in a dispersed GHE presence in northern, central and southern Italy. One of the most critical points was related to the nature of "elective" courses, which were not mandatory in the curricula. Enrollees tended to be students genuinely interested in GH issues. Some community and service-learning experiences, referred to as GH gyms, were also detected at national and international levels. GHE has spreading in Italy in line with the vision of the Italian Network for Global Health Education. Although progress has been made to disperse GH courses around the country, more academic commitment is needed to include GH in the mandatory curricula of medical schools and other health faculties.


Isolated blastomycotic osteomyelitis: a case simulating a malignant tumor of the distal radius.
Blastomycosis osteomyelitis frequently complicates systemic blastomycosis, but it is unusual as an isolated osteolytic lesion in the asymptomatic patient. An isolated blastomycotic osteomyelitis of the distal radius was the initial manifestation of blastomycosis in a healthy young man. The lesion was originally interpreted as a sarcoma. Fungal osteomyelitis must be differentiated from radiologically similar bone neoplasms.


The pint- sized powerhouse: Illuminating the mighty role of the gut microbiome in improving the outcome of anti- cancer therapy.
Cancer persists as a major health catastrophe and a leading cause of widespread mortality across every nation. Research of several decades has increased our understanding of the pivotal pathways and key players of the host during tumor development and progression, which has enabled generation of precision therapeutics with improved efficacy. Despite such tremendous advancements in our combat against this fatal disease, a majority of the cancer patients suffer from poor tumor- free survival owing to the increased incidence of recurrent tumor. This is primarily due to the development of resistance against contemporary anti- cancer strategies. Recent studies have pointed towards the involvement of the human symbiotic gut microbiota in regulating the outcome of chemotherapy and immunotherapy. It does so primarily by modulating the metabolism of the drugs and host immune response, thereby enhancing the efficacy and ameliorating the toxicity. The interactions between the therapeutic agents, microbial community and host immunity may provide a new avenue for the clinical management of cancer. In addition, consumption of dietary pro-, pre- and synbiotics has been recognized to confer protection against tumor genesis and also promote improved response to traditional tumor suppressive strategies. Naturally, the use of various combinatorial regimes containing dietary supplements that improve the gut microbiome in amalgamation with conventional cancer treatment methods may significantly augment the therapeutic outcome of cancer patients and circumnavigate the resistance mechanisms that confound traditional therapies. In this review, we have summarized the role of the gut microbiome, which is the largest assembly of commensals within the human body, in regulating the efficacy and toxicity of various existing anti- cancer therapies including chemotherapy, immunotherapy and surgery. Furthermore, we have discussed how novel strategies integrating the application of probiotics, prebiotics, synbiotics and antibiotics in combination with the aforementioned anti- cancer modules manipulate the gut microbiota and, therefore, augment their therapeutic outcome. Together, such innovative anti- tumorigenic approaches may prove highly effective in improving the prognosis of cancer patients.


Population-based study of acquired cerebellar ataxia in Al-Kharga district, New Valley, Egypt.
The aim of this research was to determine the prevalence and etiology of acquired ataxia in Al-Kharga district, New Valley, Egypt. A population-based study of acquired ataxia was conducted in a defined geographical region with a total population of 62,583. A door-to-door survey was used to identify cases of acquired cerebellar ataxia. Patients with acquired cerebellar ataxia at any age and of both genders were included. Cases of known inherited cerebellar ataxia, acquired neurological disorders with ataxia as a minor feature, or pure acquired sensory ataxia, were excluded. We identified 17 cases of acquired ataxia, of which eight were vascular, six were an ataxic cerebral palsy subtype, and three involved postencephalitic ataxia. The crude prevalence rate for acquired ataxia was 27.16/100,000 (95% confidence interval [CI]: 14.3-40.1). The mean age of the patients at interview was 31.8 (range 4-72) years, with a male to female ratio of 2.1:1. The most frequent presenting complaint was disturbance of gait (90.7%). The majority (92%) were ambulatory, but only 9.3% were independently self-caring. This population-based study provides an insight into acquired cerebellar ataxia within a defined region, and may inform decisions about the rational use of health care resources for patients with acquired cerebellar ataxia. The most common causes of acquired cerebellar ataxia in this region were cerebrovascular injury and cerebral palsy.


Plasma deoxycholic acid is related to deoxycholic acid in faecal water.
Bile acids are considered as a risk factor for colorectal carcinogenesis. They were analysed in samples of faecal water and plasma of fasting heparine blood from 23 urolithiasis patients. Linear regression showed that the highest percentage of variance (52%) was explained by the model: plasma deoxycholic acid (micromol/l) = -3.11 + 0.96(+/-0.25*) 10log deoxycholic acid in faecal water (micromol/l) + 0.35(+/-0.15*) pH of faecal water -0.41(+/-0.19#) defacation frequency (number of stools/day); *P < 0.05, #P = 0.055. In future studies, analysing blood levels of unconjugated deoxycholic acid may substitute faecal measurements.


Development of a high throughput optical density assay to determine fungicide sensitivity of oomycetes.
A high-throughput assay was developed to screen Phytophthora species for fungicide sensitivity using optical density measurements for unbiased, automated measurement of mycelial growth. The efficacy of the optical density assay (OD) to measure phosphite sensitivity in Phytophthora species was compared to two widely used methods, radial growth (RG) and dry weight (DW) assays. Three isolates of each of Phytophthora cinnamomi, P. multivora and P. pluvialis, with known phosphite exposure and three isolates of each species with no prior phosphite exposure, were screened for phosphite sensitivity using the three assays. Mycelial growth measurements were taken after culturing for 6, 14 and 15 days for the OD, DW and RG assays respectively. Mycelial growth inhibition at 15, 80, 200 and 500 μg/mL phosphite relative to growth on control media was used to determine effective concentration values for 50% growth reduction (EC50). The species varied in their tolerance to phosphite with P. cinnamomi being the least sensitive followed by P. multivora and P. pluvialis. No significant differences in tolerance were found between isolates within the same species using any method. The OD assay produced comparable EC50 values to the RG and DW assays. The growth of the three species was more sensitive to phosphite in the DW than the RG and OD assays, however limited sample throughput and greater variation in measuring small amounts of mycelia in the dry weight assessment increase variability and limits throughput. The OD assay offers a fast method to enable an inventory of chemical resistance and is particularly advantageous for slow growing species as it requires less time and offers greater throughput than existing RG and DW methods.


An endoscopic endonasal approach for the surgical repair of transsphenoidal cephalocele in children.
Transsphenoidal cephalocele is a rare lesion traditionally managed by either an intracranial approach or by a combined intracranial and extracranial approach. A two-year-old boy presented with a transsphenoidal cephalocele manifesting as apneic-cyanotic spells accompanied by breathing difficulties due to nasal obstruction after birth. Neuroimaging revealed a cystic mass extending from the pituitary fossa into the nasopharynx through the sphenoid sinus. Nasal endoscopy confirmed the diagnosis of transsphenoidal meningocephalocele. The lesion was managed with an endoscopic endonasal approach. The cephalocele and its contents were passively reduced by applying bipolar cautery to the overlying mucosa. Once reduced, the mucosa was incised and removed from the underlying dura to allow further reduction of the dural sac and its contents. The dural sac was amputated partially using microscissors, followed by repair of the dural defect. The patient developed mild diabetes insipidus after surgery. Follow-up evaluation demonstrated resolution of the preoperative symptoms without lasting morbidity. This procedure is safe, less time consuming than the transcranial approach, and efficacious.


Enhanced sensory convergence to the visual cortex in the rodless (rd/rd) mouse.
The rd/rd mutation provokes a specific degeneration of the photoreceptive cells in the mouse retina, without affecting other neuronal elements. This degeneration starts 8 to 10 days after birth. Discriminative learning experiments have shown the degenerated retina to remain light-sensitive, the sensitivity being reduced to 10(-5) of normal with a peak still at 500 nm. An ontogenetic study showed a progressive vanishing of visual potentials (electroretinogram and visual evoked potentials) during the third week of life. Potentials of auditory origin, which can be recorded from the visual cortex in normal mice, were found to be clearly facilitated by the absence of the visual input either because of retinal degeneration in rd mouse or provoked by enucleation at birth.


Cyclic AMP and ultrastructural organization of the nerve cell nucleus: stimulation of nuclear microtubules and microfilaments assembly in sympathetic neurons.
As we have previously shown for electrical stimulation, in vivo cyclic AMP analogues and theophylline induce an increase (up to 8.5-fold) in the frequency of microtubular-microfilamentous inclusions in the nucleus of sympathetic neurons. These drugs, like electrical stimulation, do not modify the ultrastructural organization of such inclusions, which is briefly reviewed in the present study with the help of tilting experiments. Such data consistent with our previous opinion that microtubules and microfilaments are normal nuclear constituents of these nerve cells, their frequency being related to physiological activity. Moreover, our results may now be discussed in terms of the relationship between these nuclear inclusions and the physiological modulation of transmission through the sympathetic ganglion. Finally, as recently demonstrated in the cytoplasm, the present study shows for the first time that cyclic AMP promotes the assembly of microtubules and microfilaments in the nuclear compartment.


The safety and efficacy of systemic versus catheter-based therapies: application of a prognostic model by a pulmonary embolism response team.
The decision by pulmonary embolism response teams (PERTs) to utilize anticoagulation (AC) with or without systemic thrombolysis (ST) or catheter-directed therapies (CDT) for pulmonary embolism (PE) is a balance between the desire for a positive outcome and safety. Our primary aim was to develop a predictive model of in-hospital mortality for patients with high- or intermediate-risk PE managed by PERT while externally validating this model. Our secondary aim was to compare the relative safety and efficacy of ST and CDT in this cohort. Consecutive patients hospitalized between June 2014 and January 2020 at the Cleveland Clinic Foundation and The University of Rochester with acute high- or intermediate-risk PE managed by PERT were retrospectively evaluated. Groups were stratified by treatment strategy. The primary outcome was in-hospital mortality, and secondary outcome was major bleeding. A logistic regression model to predict the primary outcome was built using the derivation cohort, with 100-fold bootstrapping for internal validation. External validation was performed and the area under the receiver operating curve (AUC) was calculated. Of 549 included patients, 421 received AC alone, 71 received ST, and 64 received CDT. Predictors of major bleeding include ESC risk category, PESI score, hypoxia, hemodynamic instability, and serum lactate. CDT trended towards lower mortality but with an increased risk of bleeding relative to ST (OR = 0.42; 95% CI [0.15, 1.17] and OR = 2.14; 95% CI [0.9, 5.06] respectively). In the multivariable logistic regression model in the derivation institution cohort, predictors of in-hospital mortality were age, cancer, hemodynamic instability requiring vasopressors, and elevated NT-proBNP (AUC = 0.86). This model was validated using the validation institution cohort (AUC = 0.88). We report an externally-validated model for predicting in-hospital mortality in patients with PE managed by PERT. The decision by PERT to initiate CDT or ST for these patients had no impact on mortality or major bleeding, yet the long-term efficacy of these interventions needs to be elucidated.


Nisin Induces Cell-Cycle Arrest in Free-Living Amoebae Acanthamoeba castellanii.
Acanthamoeba spp. are free-living amoebas with worldwide distribution and play an important role as disease-causing agents in humans. Drug inability to completely eradicate these parasites along with their toxic effects suggest urgent need for new antimicrobials. Nisin is a natural antimicrobial peptide produced by Lactococcus lactis. Nisin is also the only bacteriocin approved for use in food preservation. In this work, we analyzed the effect of nisin on the growth of Acanthamoeba castellanii trophozoites. A total of 8 × 104 trophozoites were exposed to increasing concentrations of nisin to determine its activity. Changes in cell membrane and cellular cycle of trophozoites were investigated by flow cytometry, and nisin cytotoxicity in mammalian cells was evaluated in L929 cells by MTT method. After 24 h exposure to increasing nisin concentrations, an IC50 of 4493.2 IU mL-1 was obtained for A. castellanii trophozoites. However, after 72 h a recovery in amoebic growth was observed, and it was no longer possible to determine IC50. Flow cytometry analysis showed that nisin has no effect on the membrane integrity. Treatment with nisin induced cell-cycle arrest during G1 and S phases in A. castellanii trophozoites, which recovered their growth after 72 h. This is one of the first studies showing the effect of internationally approved nisin against A. castellanii trophozoites. Nisin caused cell-cycle arrest in trophozoites, momentarily interfering with the DNA replication process. The data highlight the amoebostatic activity of nisin, and suggest its use as an adjuvant for the treatment of infections caused by Acanthamoeba spp.


Two-step separation of human peripheral blood monocytes on discontinuous density gradients of colloidal silica-polyvinylpyrrolidinone.
Normal human peripheral blood monocytes were purified by a two-step separation. The first step, the standard Ficoll--Hypaque (F--H) buoyant density centrifugation, yielded mainly mononuclear cells, of which 24 +/- 9% were monocytes. Isopycnic centrifugation on discontinuous gradients of colloidal silica polyvinylpyrrolidinone (CS-PVP) further separated these mononuclear cells. The density interface between 1.070 and 1.060 g/ml yielded 82 +/- 7% monocytes, 5 +/- 4% granulocytes and 13 +/- 8% lymphocytes. Sixty-six percent of the monocytes obtained after F--H separation were recovered in this layer. The monocytes were intact and viable and retained their ability to phagocytose and kill Candida pseudotropicalis and to spread on glass coverslips. Motility (both random and towards a chemoattractant) was retained but was quantitatively less than after F--H separation alone. The relative purity of the monocyte population allowed assessment of major histocompatibility surface antigens by serotyping. This confirmed the presence of HLA and Ia-like antigens on monocytes.


Maintaining mental health in the time of coronavirus.
From social isolation to working on the front line, covid-19 is posing serious challenges to mental health. Moya Sarner asks the experts how we can protect ourselves.


Communication and professionalism.
The text of this lecture was presented in July 1999 at the international Chicago meeting on Communication in Medicine. The topic 'Communication and professionalism' has been approached by drawing on the work at the Association of American Medical Colleges (AAMC). The challenge is to align medical education content with societal needs, practice patterns and scientific developments. In this perspective, the goals of medicine have been presented, however, also related to experienced real life situations, the changes within medical practice and the erosion of the doctor-patient relationship. It is stressed that we must produce excellent clinicians, who have good communication skills, and being able to use those skills in the care of their patients. This implies that the current focus on communication in medicine is very important in the medical education.


Interaction between human cervical mucus and sperm surface antibodies.
The immunobead test was used to study the immunoglobulin class of antibodies on sperm before and after penetration through a microcolumn of cervical mucus. Sixteen men with positive sperm antibodies (positive sperm immobilization test) and sperm that penetrated cervical mucus in prior tests were selected for study. However, at the time of study, sperm from seven subjects could not be recovered from the microcolumn. The nine subjects from whom motile sperm were obtained after passage through the column had better sperm mucus penetration tests, lower proportions of sperm binding to anti-IgA immunobeads, and higher proportions of sperm with tail-tip-only binding. Sperm recovered after penetration through the mucus microcolumn displayed a greatly reduced binding to anti-IgA immunobeads in all nine subjects, whereas similar reductions in anti-IgG binding occurred only in four subjects. These results confirm that IgA and sperm-head-directed antibodies are more important than IgG and sperm tail-tip-directed antibodies in impairing sperm penetration of cervical mucus.


Surgical Drill Guide for Insertion of an Infra-Acetabular Screw Based on an Anatomically Precontoured Plate System: A Cadaveric Study.
Due to the anatomic structure of the pelvis, free-hand placement of screws in the acetabular fracture management can be difficult. Infra-acetabular screw fixation increases acetabular stability by distal fixation of the cup. Aim of this cadaveric study is to investigate if a plate-referenced drill guide can provide save placement of an infra-acetabular screw over a precontoured suprapectineal quadrilateral buttress plate (SQBP). We constructed a drill guide for an infra-acetabular screw based on the surface of an anatomically precontoured SQBP. A total of 12 adult cadaveric acetabular specimens were used for drill guide-assisted placement of the infra-acetabular screw. The drill guide contains a radiopaque spiral to allow longitudinal fine adjustment of the SQBP along the pelvic brim to assure correct position of the plate-drill-guide construct in relation to the Koehler's teardrop. After screw placement, we conducted a computed tomography (CT) scan of all specimens to assess the actual position of the screw in relation of the infra-acetabular corridor and the acetabular joint surface. The position of the screw was within the infra-acetabular corridor in all cases. We did not see any intra-articular or intrapelvic screw penetration. The mean distance of the centerline of the screw to the medial border of the infra-acetabular corridor was 3.35 mm. The secure distance to the virtual surface of the femoral head to was 7.3 mm. A plate-referenced drill guide can provide safe placement of an infra-acetabular screw for treatment of acetabular fractures. Radiographic fine adjustment is necessary to access the optimal entry point.


Enzyme histochemistry of rat folic acid nephropathy.
One hour after a single i.v. dose of 250 mg/kg folic acid, the straight portion of distal tubules in the outer medulla of rat kidneys showed a distinct reduction in succinate dehydrogenase, NADH2-diaphorase, glutamate dehydrogenase, cytochrome oxydase, Na+/K+-ATPase, and acid phosphatase activity. In contrast, the proximal tubules exhibited only a reduction in glutamate dehydrogenase and alkaline phosphatase activity. At this time the straight portion of the distal tubules, whose enzyme activity had changed, showed partly regressive epithelial changes. 24 hours after folic acid administration an even greater reduction in enzyme activity had occurred in the straight portion of distal tubules; these structures also became dilated. The adjacent collecting tubules and the corresponding proximal tubules were also severely dilated, the proximal tubules showing a loss in enzyme acitivities similar to those observed in the distal tubules. 48 hours after folic acid administration the changes largely resembled those observed after 24 hours, but were more pronounced. At this time a tubular regeneration was observed. 72 hours after folic administration extensive normalization of the histological and histochemical changes had occured. It is postulated that a disturbance of the hairpin counter-current mechanism occurs as a result of a direct, concentration-dependent effect of folic acid on the enzymes of the energy supplying metabolism. A dilation in the region of the loop of Henle and the collecting tubules occurs subsequently.


Clinical experience on follicular unit extraction megasession for severe androgenetic alopecia.
Severe androgenetic alopecia has significant impact on patients' self-image and emotional health. As the most advanced way to achieve the growth of a full head of hair in shortest period of time, the megasession hair transplant procedure is a promising treatment for severe androgenetic alopecia. To introduce the procedure and technical details of follicular unit extraction megasession and to evaluate the surgery outcome. A total of 273 male patients undergoing follicular unit extraction (FUE) megasession between 2016 and 2018 were included in our study. The extraction was performed using 1.0 mm punch. The BASP classification degree of patient hair loss, the number of extracted hair, surgery consuming time, and graft survival rate were recorded. We finally evaluated patients' satisfaction with surgery outcomes. Ages of patients ranged from 28 to 53 years, with a mean of 42 years (SD, 8.42). All of them were at C3 and U1 degree of BA type hair loss according to the BASP classification. The number of follicular units transplanted was between 3000 and 6000, with surgery duration range from 6 hours to 12 hours and graft survival rate varies from 93.5% to 96.6%. A total of 81% of them were satisfied with the outcomes, 19% of them had a second procedure performed to provide further hair density. None of them had infection after the surgery. Compared with multi-stage hair transplantation, FUE megasession has the advantages of reducing operation frequency and overall surgery duration. Thus, FUE megasession is an appealing treatment option for severe AGA patients, who expect to a more desirable natural and esthetically pleasing result in a one-stage operation.


Experiences of telemedicine in neurological out-patient clinics during the COVID-19 pandemic.
The COVID-19 pandemic has led to rapid changes in the delivery of medical care worldwide. The main objective of this survey was to investigate the initial experiences of neurologists with the use of telemedicine for different neurological conditions during the first phase of the COVID-19. All hospital-based neurologists in Norway (n = 400) were invited to a questionnaire survey by e-mail in April 2020. The study focused on telemedicine and all questions were answered with regard to the first weeks of the pandemic lockdown in Norway. One-hundred and thirty-five neurologists responded. Overall, 87% reported a shift toward more telemedicine, with significantly more use of telephone than video consultations for both new referrals (54% vs. 30%, P < 0.001) and follow-ups (99% vs. 50%, P < 0.001). Respondents deemed it much more professionally satisfactory to conduct follow-up consultations by telephone, than to carry out consultations with new patients by telephone (85% vs. 13%, P < 0.001). Teleconsultations were better suited for headache and epilepsy patients as compared to multiple sclerosis and movement disorder patients. There was no significant difference between residents and senior consultants regarding how they experienced teleconsultations. Female neurologists found telemedicine better and more effective than male neurologists. Telemedicine was rapidly implemented in Norwegian neurological departments during the first weeks of the COVID-19 pandemic. Teleconsultations were better suited for follow-ups than for new referrals, and better for headache and epilepsy patients as compared to multiple sclerosis and movement disorder patients.


Neurological complications of systemic cancer.
Neurological complications of systemic cancer-those arising outside the nervous system-can be distressing, disabling, and sometimes fatal. Diagnosis is often difficult because different neurological disorders may present with similar signs and symptoms. Furthermore, comorbid neurological illnesses, common in elderly patients with cancer, can complicate diagnosis. Early diagnosis and aggressive treatment can improve neurological symptoms and can substantially enhance a patient's quality of life. We approach the problem of neurological complications of systemic cancer as would a neurologist: first by identifying the anatomical area or areas that are affected (ie, brain, spinal cord, peripheral nerve), then by evaluating the diagnostic approach, considering the symptoms and signs and including appropriate laboratory tests, and finally, by recommending treatment. We focus on disorders that are difficult to diagnose, need neurological consultation, and for which effective treatments exist.


Preoperative pulmonary function and mortality after cardiac surgery.
The aim of the study was to examine the relationship between preoperative pulmonary function and outcomes after cardiac surgery. We performed preoperative pulmonary function tests (PFTs) in 1,169 patients undergoing cardiac surgery at the Minneapolis Veterans Affairs Medical Center. Airway obstruction was defined as forced expiratory volume in 1 minute (FEV(1)) to forced vital capacity ratio <0.7. Of the 1,169 patients, 483 (41%) had a prior history of chronic obstructive pulmonary disease (COPD). However, 178 patients with a history of COPD had no airway obstruction on PFT. Conversely, 186 patients without a COPD history had airway obstruction on PFT. Thus, PFT results helped reclassify the COPD status of 364 patients (31%). Operative mortality was 2% in patients with no or mild airway obstruction versus 6.7% in those with moderate or severe obstruction (ie, FEV(1) to forced vital capacity ratio <0.7 and FEV(1) <80% predicted). Postoperative mortality was higher (odds ratio 3.2, 95% CI 1.6-6.2, P = .001) in patients with moderate or severe airway obstruction and in patients with diffusing capacity of the lung for carbon monoxide <50% of predicted (odds ratio 4.9, 95% CI 2.3-10.8, P = .0001). Notably, mortality risk was 10x higher (95% CI 3.4-27.2, P = .0001) in patients with moderate or severe airway obstruction and diffusing capacity of the lung for carbon monoxide <50% of predicted. These data show that PFT before cardiac surgery reclassifies the COPD status of a substantial number of patients and provides important prognostic information that the current risk estimate models do not capture.


[False traumatic aneurysm of the ulnar artery in a teenager].
Most aneurysms of hand arteries are traumatic. It is a generally rare unrecognized pathology. Complications are serious (embolism and thromboses of interdigital arteries). Two main causes can be recalled: acute trauma, with development of a false aneurysm; repeated microtrauma (hand hammer syndrome), with occurrence of an arterial dysplasic aneurysm. The diagnosis is based on the presence of a pulsatile mass, with finger dysesthesia, unilateral Raynaud's phenomenon. It is confirmed by duplex Doppler. Arteriography is necessary but can be replaced by an angio-MR. We report a case of false traumatic aneurysm of the ulnar artery in a teenager. This case illustrates this rare condition and opens discussion on therapeutic options.


A comparison of immediate postreduction splinting constructs for controlling initial displacement of fractures of the distal radius: a prospective randomized study of long-arm versus short-arm splinting.
To compare, in a prospective, randomized manner, the sugar tong splint with a short-arm radial gutter splint in terms of patient satisfaction and the ability to maintain reduction of distal radius fractures. A total of 118 patients with displaced distal radius fractures were enrolled; 85 patients (85 fractures) were available for follow-up evaluation and were included in the study population. There were 26 men and 59 women with a mean age of 64 years. Thirty-eight fractures were immobilized in a short-arm radial gutter splint and 47 in a sugar tong splint. Forty fractures had a stable pattern and 45 had an unstable fracture pattern. The initial patient follow-up examination occurred a mean of 8 days after splint application. A total of 33 fractures showed loss of fracture reduction at the initial follow-up evaluation. Sixteen of 38 fractures immobilized with the radial gutter splint displaced, whereas displacement was seen in 17 of 47 fractures immobilized with a sugar tong splint; this difference was not significant. When the splint constructs were evaluated based on fracture stability no differences were found between the splints' ability to maintain fracture reduction in both stable and unstable displaced fractures. Patients in the short-arm radial gutter splint group had significantly better Disabilities of the Arm, Shoulder, and Hand scores than those patients whose fractures were immobilized with a sugar tong splint. Both the sugar tong splint and the short-arm radial gutter splint had comparable performance in maintaining the initial reduction of distal radius fractures, with the short-arm splint tolerated better by patients. Based on our study we recommend the use of a short-arm radial gutter splint for initial immobilization of displaced distal radius fractures. Prognostic, level II.


Chemical conversion of anthramycin 11-methyl ether to didehydroanhydroanthramycin and its utilization in studies of the biosynthesis and mechanism of action of anthramycin.
Reaction of anthramycin 11-methyl ether (AME) with trifluoroacetic acid results in formation of (1,11a)-didehydroanhydroanthramycin (DAA). Anthramycin biosynthetically labelled from DL-[3'RS(3'-3H)]; DL-[3'S(3'-3H)] and DL-[3'R(3'-3H)] tyrosine each lose approximately 50% of their tritium during this conversion to DAA confirming the labelling pattern of 3'-tritiated species of tyrosine in AME. As expected negligible losses of tritium occurred from AME biosynthetically labelled fron L-[2- or 6-3H] or L-[3- or 5-3H]tyrosine. DAA did not form a stable adduct with DNA in accord with the postulated mechanism of action of anthramycin.


MicroRNAs in amniotic fluid and maternal blood plasma associated with sex determination and early gonad differentiation in cattle†.
We hypothesized that sexually dimorphic differences exist in the expression of miRNAs in amniotic fluid (AF) and maternal blood plasma (MP) in association with the process of sex determination and gonad differentiation in cattle. Amniotic fluid and MP were collected from six pregnant heifers (three carrying a single male and three a single female embryo) following slaughter on Day 39 postinsemination, coinciding with the peak of SRY expression. Samples (six AF and six MP) were profiled using an miRNA Serum/Plasma Focus PCR Panel. Differentially expressed (DE) miRNAs were identified in AF (n = 5) and associated MP (n = 56) of male vs. female embryos (P < 0.05). Functional analysis showed that inflammatory and immune response were among the 13 biological processes enriched by miRNAs DE in MP in the male group (FDR < 0.05), suggesting that these sex-dependent DE miRNAs may be implicated in modulating the receptivity of the dam to a male embryo. Further, we compared the downstream targets of the sex-dependent DE miRNAs detected in MP with genes previously identified as DE in male vs. female genital ridges. The analyses revealed potential targets that might be important during this developmental stage such as SHROOM2, DDX3Y, SOX9, SRY, PPP1CB, JARID2, USP9X, KDM6A, and EIF2S3. Results from this study highlight novel aspects of sex determination and embryo-maternal communication in cattle such as the potential role of miRNAs in gonad development as well as in the modulation of the receptivity of the dam to a male embryo.


Role of serum albumin and proteinuria in patients with SARS-CoV-2 pneumonia.
Hypoalbuminemia is frequently observed in patients with SARS-CoV-2 infection although its underlying mechanism and relationship with the clinical outcome still need to be clarified. We retrospectively evaluated in patients with COVID-19 hospitalised at the Fatebenefratelli-Sacco Hospital in Milan, the prevalence of hypoalbuminemia, its association with the severity of COVID-19, with the levels of C-reactive protein, d-dimer and interleukin-6 and with clinical outcome over a follow-up period of 30 days. Urinalysis was evaluated in a subgroup of patients. Serum albumin levels <30 g/L were found in 105/207 (50.7%) patients at hospital admission. Overall, the median albumin value was 29.5 g/L (IQR 25-32.8). A negative association was found between albumin levels and severity of COVID-19 (P < .0001) and death (P = .003). An inverse correlation was observed between albumin and both C-reactive protein and D-dimer at hospital admission (r = -.487 and r = -.479, respectively; P < .0001). Finally, a positive correlation was found between albumin levels and eGFR (r = .137; P = .049). Proteinuria was observed in 75% of patients with available data and it did not differ between patients with hypoalbuminemia and those with albumin ≥30 g/L (81% and 67%, respectively; P = .09). In patients with COVID-19, hypoalbuminemia is common and observed in quite an early stage of pulmonary disease. It is strictly associated with inflammation markers and clinical outcome. The common finding of proteinuria, even in the absence of creatinine increase, indicates protein loss as a possible biomarker of local and systemic inflammation worthwhile to evaluate disease severity in COVID-19.


Controlling the Oxidation State of Pt Single Atoms for Maximizing Catalytic Activity.
Single-atom catalysts (SACs) have emerged as promising materials in heterogeneous catalysis. Previous studies reported controversial results about the relative level in activity for SACs and nanoparticles (NPs). These works have focused on the effect of metal atom arrangement, without considering the oxidation state of the SACs. Here, we immobilized Pt single atoms on defective ceria and controlled the oxidation state of Pt SACs, from highly oxidized (Pt0 : 16.6 at %) to highly metallic states (Pt0 : 83.8 at %). The Pt SACs with controlled oxidation states were then employed for oxidation of CO, CH4 , or NO, and their activities compared with those of Pt NPs. The highly oxidized Pt SACs presented poorer activities than Pt NPs, whereas metallic Pt SACs showed higher activities. The Pt SAC reduced at 300 °C showed the highest activity for all the oxidations. The Pt SACs with controlled oxidation states revealed a crucial missing link between activity and SACs.


Pediatric pulmonology year in review 2020: Physiology.
Pulmonary physiology is a core element of pediatric pulmonology care and research. This article reviews some of the notable publications in physiology that were published in Pediatric Pulmonology in 2020.


Growth hormone treatment and bone mineral density in pediatric patients with Prader-Willi syndrome.
Previous reports indicate that growth hormone (GH) treatment for Prader-Willi syndrome (PWS) improves bone mineral density (BMD) only when initiated at a young age and not when initiated in adulthood. However, there are no data on BMD during long-term GH treatment of Japanese children and adolescents with PWS. Thus, this study aimed to investigate BMD changes among patients with PWS, who were undergoing GH treatment from childhood to adolescence. Sixty-seven pediatric patients with PWS who had GH treatment initiated during childhood between January 2003 and June 2020 were evaluated. To avoid underestimation, we used total body BMD, which was evaluated using dual-X-ray absorptiometry adjusted for the BMD z-score using patient height, sex, and age. In both sexes, age was negatively correlated with the BMD-standard deviation score (SDS) (male: r=-0.156 [p=0.042]; female: r=-0.197 [p=0.043]), which started to decrease in childhood. The BMD-SDS of patients with PWS decreases gradually despite GH treatment. As there are no clear recommendations about monitoring of bone health in patients with PWS, further studies are needed to improve the guidelines for screening of BMD and treatment of patients with PWS.


A cross-industry collaboration to assess if acute oral toxicity (Q)SAR models are fit-for-purpose for GHS classification and labelling.
This study assesses whether currently available acute oral toxicity (AOT) in silico models, provided by the widely employed Leadscope software, are fit-for-purpose for categorization and labelling of chemicals. As part of this study, a large data set of proprietary and marketed compounds from multiple companies (pharmaceutical, plant protection products, and other chemical industries) was assembled to assess the models' performance. The absolute percentage of correct or more conservative predictions, based on a comparison of experimental and predicted GHS categories, was approximately 95%, after excluding a small percentage of inconclusive (indeterminate or out of domain) predictions. Since the frequency distribution across the experimental categories is skewed towards low toxicity chemicals, a balanced assessment was also performed. Across all compounds which could be assigned to a well-defined experimental category, the average percentage of correct or more conservative predictions was around 80%. These results indicate the potential for reliable and broad application of these models across different industrial sectors. This manuscript describes the evaluation of these models, highlights the importance of an expert review, and provides guidance on the use of AOT models to fulfill testing requirements, GHS classification/labelling, and transportation needs.


Everyone knows what behavior is but they just don't agree on it.
Studying "behavior" lies at the heart of many disciplines. Nevertheless, academics rarely provide an explicit definition of what "behavior" actually is. What range of definitions do people use, and how does that vary across disciplines? To answer these questions, we have developed a survey to probe what constitutes "behavior." We find that academics adopt different definitions of behavior according to their academic discipline, animal model that they work with, and level of academic seniority. Using hierarchical clustering, we identify at least six distinct types of "behavior" which are used in seven distinct operational archetypes of "behavior." Individual respondents have clear consistent definitions of behavior, but these definitions are not consistent across the population. Our study is a call for academics to clarify what they mean by "behavior" wherever they study it, with the hope that this will foster interdisciplinary studies that will improve our understanding of behavioral phenomena.


Breast-feeding and the potential for human immunodeficiency virus transmission.
There is evidence to suggest that the human immunodeficiency virus (HIV) can be transmitted from mothers to their uninfected offspring via infected breast milk. The quantitative risk of transmission by this route is unknown. We must urge all individuals at risk for HIV infection to be tested. In the United States, it is recommended that women who are known to be HIV-positive be discouraged from breast-feeding. In certain regions of the United States, such as high-risk areas of New York City, HIV infection may be present in more than 3% of reproductive-age women, most of whom do not know they are infected. Women who either live in areas of the United States in which acquired immunodeficiency syndrome (AIDS) is endemic or are living in other parts of the country and are at high risk for AIDS, yet refuse to be tested, should be counseled regarding the potential for transmission of the virus to uninfected offspring via breast-feeding.


Characteristic of complete mitochondrial genome and phylogenetic relationship of a Chinese Serow in Xishui, China.
In this study, we reported a complete mitochondrial genome of Chinese Serow from Guiyang. It has a circular genome of 16,442 bp including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA genes, and a control region. In the phylogenetic tree, we found it clustered tightly with a sequence with a distinct white forehead and white face outlook in the genus Capricornis, which indicated there are a certain number of this species.


Mycobacterial RNA. A comparison with intact mycobacteria for suppression of murine tumor growth.
Our experimental data imply the following: (1) An RNA-rich fraction isolated from H37Ra, and intact H37Ra, are effective agents for suppression of tumor growth. (2) For suppression of two chemically-induced tumors with both RNA and H37Ra, direct contact with tumor is necessary. This may not be the case with other tumors in different strains of syngeneic mice. (3) The host's immunological system is a necessary component for inhibition of tumors by our test materials since there is no tumor suppression in immunologically impaired mice.


Reliability of the parallel walk test for the elderly.
To determine interrater agreement and test-retest reliability of the parallel walk test (PWT), a simple method of measuring dynamic balance in the elderly during gait. Cohort study. Outpatient clinic. Elderly fallers (N=34; mean ± SD age, 81.3±5.4y) registered at a falls clinic participated in this study based on Mini-Mental State Examination and Barthel Index scores. Subjects were timed as they walked 6m between 2 parallel lines on the floor at 3 different widths (20, 30.5, 38cm) wearing their own footwear. They were scored for foot placement on (1 point) or outside the lines (2 points) by 2 separate raters. Fifteen subjects were retested 1 week later. Footfall score and time to complete the PWT. Intraclass correlation coefficients (ICCs) and 95% limits of agreement were calculated for interrater and test-retest reliability. For widths of 20, 30.5, and 38cm, interrater reliability ICC range was .93 to .99 and test-retest ICC range was .63 to .90. The PWT was implemented easily by 2 raters with a high degree of interrater reliability. Test-retest reliability was not as high, possibly because of the high susceptibility of variation from 1 week to the next for frail elderly subjects. The 20- and 30.5-cm widths are recommended for future use of the PWT.


Isolation and partial characterization of two abnormal human plasma lipoproteins: LP-X1 and LP-X2.
Two abnormal lipoproteins (LP-X1 and LP-X2) rich in free cholesterol and phospholipid have been isolated from the plasma of nine different patients with obstructive jaundice. As isolated, both lipoproteins were devoid of low density lipoproteins as judged by agar electrophoresis. In addition, they were free of apoB as judged by double immunodiffusion. However, LP-X1 exhibited a higher phospholipid to protein ratio and a lower hydrated density than LP-X2. The levels of LP-X1 and LP-X2 in plasma were measured in three patients studied for 14 days after corrective surgery for obstructive liver disease. The level of both these abnormal lipoproteins decreased after surgery until the twelfth day when they were completely absent from the plasma of these patients. The rates of this decrease for the two particles are significantly different. These differences in metabolic, chemical, and physical properties of LP-X1 and LP-X2, establish their identity as two distinct and unique lipoprotein particles.


CT findings of regression in intraabdominal desmoplastic small-cell tumor.
We report the computed tomographic (CT) findings in a patient with intraabdominal desmoplastic small-cell tumor before and after 10 weeks of chemotherapy. This tumor is a rare, frequently fatal neoplasm of the peritoneum, seen predominantly in young males. Initial CT demonstrated large intraperitoneal masses, hepatic metastases, retroperitoneal and right axillary lymphadenopathy, ascites, and pleural effusion. Follow-up CT showed marked decrease of the main tumor bulk and complete regression in the axillary nodes.


Quality of Life of Parents of Very Low Birth Weight Babies Admitted to the Neonatal Intensive Care Unit.
This prospective cohort study was conducted at our tertiary care center from October, 2021 to April, 2022 to compare the parents' health-related quality of life (HRQoL) scores during neonatal intensive care unit (NICU) stay and at 3 months follow-up. Pediatric quality of life inventory (PedsQL) family impact module questionnaires were used in 46 mothers and 39 fathers during NICU stay, and 42 mothers and 38 fathers at 3-month follow-up. Greater proportions of mothers were severely affected and had higher stress levels as compared to fathers both during NICU stay (67.3% vs 48.7%) and at 3 months follow-up (62.7% vs 52.6%). Among the mothers, there was a significant improvement in individual and family functioning median (IQR) HRQL scores at 3-month follow-up [62 (48-83) vs 71(63-79)]. However, the pro-portion of mothers severely affected remained the same at NICU stay and 3-month follow-up (67.3% vs 62.7%).


The effect of medium composition on the production of valine by Corynebacterium 9366 - EMS/184.
The auxotrophic mutant Corynebacterium 9366-EMS/184, requiring isoleucine accumulates about 22 g of L-valine per litre after a 96 h cultivation in a medium containing 15% sucrose and 1% ammonium acetate.


SXT and Taxo A disks for presumptive identification of group A and B streptococci in throat cultures.
A bacitracin (0.04 units, BBL)-SXT (trimethoprim, 1.25 mg, plus sulfamethoxazole, 23.75 mg, BBL) susceptibility test was 94% accurate in presumptively identifying streptococci as either group A, B or not group A and B.


Stress, Mental Health, and Coping Among Workers in the Northern California Cannabis Industry: A Qualitative Descriptive Analysis.
California is home to a multibillion-dollar cannabis (marijuana) industry, but little is known about the occupational health and safety hazards faced by cannabis workers and even less of the stress, mental health, and coping mechanisms among these workers. Previous research has been based on long-term workers at legal businesses, but most California cannabis is produced and sold unlawfully. There are many seasonal workers whose experiences have not been studied. A qualitative study based on focus group discussions and key informant interviews was performed to understand cannabis workers' experiences, knowledge, and perceptions of occupational hazards. Participants reported sources of stress including production pressure and isolation, and mental health outcomes such as depression and mental fatigue. They described primarily maladaptive coping mechanisms. Unique characteristics of the cannabis industry, including criminalization and isolated, remote farms, make interventions challenging. However, policy approaches that involve community organizations could promote worker health.


Ecotoxicological impact of sunlight assisted photoreduction of hexavalent chromium present in wastewater with zinc oxide nanoparticles on common Anabaena flos-aquae.
Hexavalent chromium is more toxic and carcinogenic compared to its trivalent counterpart. Hexavalent chromium can be photocatalytically reduced to trivalent one using zinc oxide semiconductor and solar or UV radiation as light source. But an important ecological aspect is whether the net toxicity decreases after the photocatalytic process. In the present work, we have selected Anabaena flos-aquae as the model organism and examined whether the net toxicity to which it has been exposed in water decreases after photocatalytic reduction of hexavalent chromium using ZnO semiconductor as photocatalyst. We have studied the cumulative toxicities of both chromium (before and after treatment) and ZnO (both nano and micro) separately and as a suspension of ZnO in chromium. Quantitative cell surface roughness analysis was conducted using AFM to confirm the changes in cell surface properties.


Nuclear action of FGF members in endocrine-related tissues and cancer: Interplay with steroid receptor pathways.
Dysregulation of the fibroblast growth factors/fibroblast growth factor receptor (FGF/FGFR) pathway has been implicated in a wide range of human disorders and several members have been localized in the nuclear compartment. Hormone-activated steroid receptors or ligand independent activated receptors form nuclear complexes that activate gene transcription. This review aims to highlight the interplay between the steroid receptor and the FGF/FGFR pathways and focuses on the current knowledge on nuclear action of FGF members in endocrine-related tissues and cancer. The nuclear trafficking and targets of FGF/FGFR members and the available evidence on the interplay with steroid hormones and receptors is described. Finally, the data on aberrant FGF/FGFR signaling is summarized and the nuclear action of FGF members on endocrine resistant breast cancer is highlighted. Identifying the mechanisms underlying FGF-induced endocrine resistance will be important to understand how to efficiently target endocrine-related diseases and even enhance or restore endocrine sensitivity in hormone receptor positive tumors.


A pilot study on ex vivo expanded autologous adipose-derived stem cells of improving fat retention in localized scleroderma patients.
In patients with localized scleroderma (LoS), facial deformity induced by subcutaneous atrophy greatly reduces life quality. Autologous fat grafting (AFG) is used for volume restoration but with low-fat retention due to various reasons. Adipose-derived stem cells (ADSCs) have shown potential effects in improving fat retention. We aimed to compare the feasibility and efficacy of improving fat retention in LoS patients among the ADSCs-assisted, the stromal vascular fraction (SVF)-assisted and conventional AFG methods. A pilot study with a 6-month follow-up among 18 LoS patients was conducted. Participants were randomly assigned into three AFG groups: conventional group, SVF-assisted group, and ADSCs-assisted group. The SVF-assisted group received SVF-assisted AFG at the SVF:fat ratio of 1:1. The ADSCs-assisted group received the mixture of ADSCs-enriched fat graft supplemented with 5 × 105 ADSCs/mL fat. Volume retention was measured by magnetic resonance imaging, and clinical photographs were taken for outcome evaluation. At sixth-month follow-up, the fat retention of ADSCs-assisted group was 49.83 ± 3.61%, significantly higher than 31.75 ± 1.73% of SVF-assisted group (P = .0004), and 21.86 ± 1.68% of the conventional group (P < .0001). A significant difference of the fat retention was also observed between the SVF-assisted and conventional group (P = .0346). No severe adverse events occurred during the procedure and follow-up. This pilot study suggests that ADSCs-assisted AFG is a safe, feasible, and attractive alternative to conventional and SVF-assisted AFG in the correction of facial atrophy of LoS patients. Future studies with large patient samples are needed for confirmation. (Chinese Clinical Trial Registry, ChiCTR1900025717).


Architecture-Aware Modeling of Pedestrian Dynamics.
The spread of infectious diseases arises from complex interactions between disease dynamics and human behavior. Predicting the outcome of this complex system is difficult. Consequently, there has been a recent emphasis on comparing the relative risks of different policy options rather than precise predictions. Here, one performs a parameter sweep to generate a large number of possible scenarios for human behavior under different policy options and identifies the relative risks of different decisions regarding policy or design choices. In particular, this approach has been used to identify effective approaches to social distancing in crowded locations, with pedestrian dynamics used to simulate the movement of individuals. This incurs a large computational load, though. The traditional approach of optimizing the implementation of existing mathematical models on parallel systems leads to a moderate improvement in computational performance. In contrast, we show that when dealing with human behavior, we can create a model from scratch that takes computer architectural features into account, yielding much higher performance without requiring complicated parallelization efforts. Our solution is based on two key observations. (i) Models do not capture human behavior as precisely as models for scientific phenomena describe natural processes. Consequently, there is some leeway in designing a model to suit the computational architecture. (ii) The result of a parameter sweep, rather than a single simulation, is the semantically meaningful result. Our model leverages these features to perform efficiently on CPUs and GPUs. We obtain a speedup factor of around 60 using this new model on two Xeon Platinum 8280 CPUs and a factor 125 speedup on 4 NVIDIA Quadro RTX 5000 GPUs over a parallel implementation of the existing model. The careful design of a GPU implementation makes it fast enough for real-time decision-making. We illustrate it on an application to COVID-19.


LncRNA-NEF suppressed oxaliplatin resistance and epithelial-mesenchymal transition in colorectal cancer through epigenetically inactivating MEK/ERK signaling.
A major cause of oxaliplatin chemoresistance in colorectal cancer (CRC) is acquired epithelial-mesenchymal transition (EMT) in cancer cells, making the cancer cells easy to metastasis and recurrence. LncRNA Neighboring Enhancer of FOXA2 (lncRNA-NEF) has been characterized as a tumor suppressor to mediate cancer metastasis in multiple cancer types. However, whether it mediated the drug resistance remains unknown. In the present study, an oxaliplatin-resistant CRC cell line (SW620R) was established and lncRNA-NEF was obviously down-regulated in this resistant cell line. The further loss and gain-of-function studies demonstrated that this lncRNA suppressed oxaliplatin resistance as well as EMT programme in vitro and inhibited metastasis in vivo. Mechanistically, lncRNA-NEF epigenetically promoted the expression of DOK1 (Downstream of Tyrosine kinase 1), a negative regulator of MEK/ERK signaling, by disrupting DNA methyltransferases (DNMTs)-mediated DNA methylation. DOK1, in turn, induced the inactivation of MEK/ERK signaling, forming the lncRNA-NEF/DOK1/MEK/ERK regulatory axis to mediate oxaliplatin resistance in CRC. Collectively, our work reveals the critical function of lncRNA-NEF in mediating the oxaliplatin chemotherapy resistance in CRC, and provides a promising therapeutic strategy for CRC patients with oxaliplatin resistance.


Short-Course Versus Long-Course Systemic Antibiotic Treatment for Uncomplicated Intravascular Catheter-Related Bloodstream Infections due to Gram-Negative Bacteria, Enterococci or Coagulase-Negative Staphylococci: A Systematic Review.
The optimal duration of systemic antimicrobial treatment for catheter-related bloodstream infections (CRBSI) is unknown. In this systematic review, we aimed to assess the efficacy of short-course treatment for CRBSI due to Gram-negative bacteria, coagulase-negative staphylococci and enterococci. We systematically searched the electronic bibliographic databases MEDLINE, EMBASE and Cochrane Library for studies published before February 2021. All studies that investigated the duration of adequate systemic antibiotic treatment in adult patients with uncomplicated intravascular catheter infections due to Gram-negative bacteria, coagulase-negative staphylococci or enterococci were eligible for inclusion. Studies including concomitant treatment with antibiotic lock therapy were excluded. The primary outcomes were clinical failure/cure, mortality and microbiologic-confirmed relapse. Seven retrospective cohort studies and one case-cohort study met the inclusion criteria. No randomized controlled studies met inclusion criteria. The quality of the included studies was low (n = 7) to moderate (n = 1). No significant differences were observed regarding mortality and microbiological relapse between short-course and long-course systemic antibiotic treatment in patients with CRBSI due to coagulase-negative staphylococci or Gram-negative bacteria. No association was found between mortality and treatment duration in the two studies assessing enterococcal CRBSI. The limited data available suggests that shorter systemic antibiotic treatment duration may be sufficient for uncomplicated CRBSI. Further well-designed prospective studies are needed to confirm these findings. CRD42021224946 (PROSPERO).


Daily inhaled flow profiles and drug release from dry powder inhalers in patients with bronchial asthma.
Inhalation flow profiles may affect particle release from dry powder inhalers (DPIs). Currently available measures include a limited number of laboratory-measured parameters such as peak inhalation flow (PIF) and inhaled volume (inhV). We aimed to investigate whether parameters obtained under such conditions are valid in real-world settings and determine the effective inhalation profile. We included seven asthmatics without recent deterioration and regularly inhaling Turbuhaler® or Diskus®. Daily inhalation profiles and particle release from either DPI were measured at home using a newly designed handy analyzer (real-life inhalation events recorder [RLEFR]), for ≥2 weeks. Inhalation pressure drop and signals of particle release during each inhalation were recorded. All patients inhaled daily with similar patient-specific profiles. The mean PIF and inhV were 91.9-31.6 L/min and 0.84-2.05 L, respectively. PIFs were smaller than those obtained in previous laboratory studies, and only one patient exceeded inhV of 2.0 L. The mean flow acceleration and particle emission were 39-571 L/min/s and 0.37-1.54 s, respectively. Particle release was sporadic in one Turbuhaler® user whose PIF was 31.6 L/min, appearing at 1.55 s of inhalation. Particle release from Turbuhaler® appeared to be PIF-dependent, but that from Diskus® was not. Inhalation flow profile measured at home is highly reproducible, but tends to be weaker and shorter than that measured in the laboratory. The results confirm that rapid inhalations from the start are required when using a DPI. RLEFR is a promising device for patient education and clinical studies. UMIN000045193.


Estimating transit time for capillary blood in selected muscles of exercising animals.
The mean minimal capillary transit time was estimated in muscles of various animals using a combination of physiological and morphometric methods. Radioactive microspheres were injected intravascularly in various animals running on a treadmill at maximum oxygen consumption rate (VO2,max) to label blood flow to individual muscles. The muscles were then removed and preserved by standard methods for electron microscopy. The volume density of mitochondria was measured to assess muscle oxidative capacity. Capillary densities in muscle cross-sections, capillary diameters and tortuosities were incorporated into an estimate of capillary volume per unit muscle mass. Mean capillary transit time (tc) in the exercising muscles was estimated by dividing mass-specific capillary volume by mass-specific blood flow. Estimates of tc ranged from values near 1 s in horse heart and thigh muscles to 0.2 s in duck gastrocnemius. The relationship between muscle blood flow and tc was hyperbolic. The experimental data indicate a limiting value of 0.2 s for transit times at very high blood flows. There was no correlation between tc and body-mass-specific VO2,max.


Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients.
Regenerating gene (Reg) product, Reg, acts as an autocrine/paracrine growth factor for beta-cell regeneration. The presence of autoimmunity against REG may affect the operative of the regenerative mechanisms in beta cells of Type 1 and Type 2 diabetes patients. We screened sera from Type 1 and Type 2 diabetes subjects for anti-REG autoantibodies, searched for correlations in the general characteristics of the subjects with the presence of anti-REG autoimmunity, and tested the attenuation of REG-induced beta-cell proliferation by the autoanitibodies. We examined the occurrence of anti-REG autoantibodies in patients' sera (265 Type 1, 368 Type 2 diabetes patients, and 75 unrelated control subjects) by Western blot analysis, and evaluated inhibitory effects of the sera on REG-stimulated beta-cell proliferation by a 5'-Bromo-2'-deoxyuridine (BrdU) incorporation assay in vitro. Anti-REG autoantibodies were found in 24.9% of Type 1, 14.9% of Type 2 and 2.7% of control subjects (P = 0.0004). There were significant differences between the autoantibody positive and negative groups in the duration of disease in the Type 1 subjects (P = 0.0035), and the age of onset in the Type 2 subjects (P = 0.0274). The patient sera containing anti-REG autoantibodies significantly attenuated the BrdU incorporation by REG (35.6 +/- 4.06% of the control), whereas the nondiabetic sera without anti-REG autoantibodies scarcely reduced the incorporation (88.8 +/- 5.10%). Anti-REG autoantibodies, which retard beta-cell proliferation in vitro, are found in some diabetic patients. Thus, autoimmunity to REG may be associated with the development/acceleration of diabetes in at least some patients.


Favorable pregnancy outcomes in two patients with systemic lupus erythematosus treated with belimumab.
Systemic lupus erythematosus (SLE) is associated with poor pregnancy outcomes and complications. Belimumab can significantly improve disease activity in patients with SLE. However, there is insufficient evidence to prove the absolute safety of belimumab treatment during pregnancy. A 37-year-old woman was diagnosed with SLE after a renal puncture biopsy in 2012. The other patient was a 25-year-old woman. She was diagnosed with SLE at 19 years of age. They were treated by standard therapy in the early stage of treatment. The first patient has multiple histories of miscarriages or abortions at different gestational ages caused by SLE activity. The other patient also has persistent thrombocytopenia due to SLE flare. In our patients, SLE was poorly controlled by standard therapy. We initiated belimumab treatment during pregnancy because the benefits of treating SLE outweighed the risks to the fetus. The first patient was admitted to the first belimumab infusion at approximately 14 weeks of gestation. The other patient was admitted to the first belimumab infusion at approximately 12 weeks of gestation. Although our patients did not show complete disease remission during belimumab treatment, neither had serious adverse reactions or adverse pregnancy events, and their babies were in good conditions at birth. We present 2 cases of pregnant women with SLE who were treated with belimumab. Both were able to deliver their babies successfully without any complications.


Effects of dopamine transporter in the ventral tegmental area on sleep recovery after propofol anesthesia in sleep-deprived rats.
Previous studies indicate that propofol can help with recovery from sleep deprivation and has anti-anxiety effects. However, the underlying neurochemical mechanism remains unclear. This study aimed to investigate the effects of dopamine transporter (DAT) in the ventral tegmental area (VTA) on sleep and anxiety recovery after propofol anesthesia in rats with 24 h total sleep deprivation (TSD). Adult male Sprague-Dawley rats were in natural sleep or sleep deprived for 24 h in a sleep deprivation rat system. The rats received propofol anesthesia (75 mg/kg, i.p.) or natural sleep. Dopamine transporter knockdown was performed by microinjection of AAV-DAT-RNAi vector. EEG was measured in each group to evaluate the subsequent sleep. The elevated plus maze test (EPMT) and open field test (OFT) were used to evaluate locomotion and anxiety level in rats. Immunofluorescence was used to verify virus location and transfection efficiency. Compared with NC group, the anxiety level of Propofol group showed no significant difference, but REM sleep decreased. Compared with the TSD group, the anxiety level of the TSD + Propofol group was reduced and the sleep recovery was closer to baseline. Compared with TSD + AAV-NC group, anxiety level and sleep time increased in TSD + AAVi group, REM increased within 24 h after sleep deprivation. The sleep time of TSD + AAVi + Propofol group was between those of TSD + AAV-NC group and TSD + AAVi group. TSD + AAV-NC + Propofol group had the least sleep time and the lowest anxiety level. 1. Propofol did not change anxiety level in normal rats, but reduced REM sleep, while it could accelerate sleep recovery and reduce anxiety level in sleep-deprived rats. 2. In sleep deprived rats with DAT knockdown, propofol improved sleep and anxiety levels more slowly, especially producing more REM rebound, suggesting that the improvement of sleep and anxiety levels in sleep-deprived rats with propofol may be related to DAT in VTA region.


Day case treatment of delayed union of fracture of the shaft of the tibia with an external fixator.
We report six cases of delayed union of fractures of the shaft of the tibia treated by the application of an external fixator on a day case basis. All fractures united within 12 weeks.


Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities.
Histamine intolerance (HIT) is associated with an excess of histamine because of an impaired function of the histamine-degrading enzyme diamine oxidase (DAO). The genetic background of HIT is unknown yet. Case-control association study of all haplotype tagging and four previously reported DAO SNPs and one HNMT Single nucleotide polymorphism with symptoms of HIT and DAO serum activity in 484 German individuals including 285 patients with clinical symptoms of HIT and 199 controls. Diamine oxidase serum activity was significantly associated with seven SNPs within the DAO gene. The minor allele at rs2052129, rs2268999, rs10156191 and rs1049742 increased the risk for a reduced DAO activity whereas showing a moderate protective effect at rs2071514, rs1049748 and rs2071517 in the genotypic (P = 2.1 × 10(-8) , 7.6 × 10(-10) , 8.3 × 10(-10) , 0.009, 0.005, 0.00001, 0.006, respectively) and allelic genetic model (P = 2.5 × 10(-11) , 5.4 × 10(-13) , 8.9 × 10(-13) , 0.00002, 0.006, 0.0003, 0.005, respectively). Reporter gene assays at rs2052129 revealed a lower promoter activity (P = 0.016) of the minor allele. DAO mRNA expression in peripheral blood mononuclear cells of homozygous carriers of the minor allele at rs2052129, rs2268999, rs10156191 was lower (P = 0.002) than homozygous carriers of the major allele. Diamine oxidase variants were not associated with the HIT phenotype per se, only with DAO activity alone and the subgroup of HIT patients displaying a reduced DAO activity. DAO gene variants strongly influence DAO expression and activity but alone are not sufficient to fully effectuate the potentially associated disease state of HIT, suggesting an interplay of genetic and environmental factors.


Thyroiditis following vaccination against COVID-19: Report of two cases and review of the literature.
Immune response following viral infections has been suggested as a probable mechanism leading to subacute thyroiditis (SAT). A few cases of SAT following SARS-CoV-2 infection have been described since the outbreak of the pandemic in 2019. Cases of SAT after vaccination against influenza have also been reported. We describe two female patients with thyroiditis after vaccination against SARS-CoV-2. The first patient presented with fever and pain in the thyroid area typical of SAT two weeks after vaccination with the BNT162B2 mRNA (Pfizer-BioNTech) COVID-19 vaccine. The second patient presented with biochemical and imaging features consistent with silent thyroiditis three weeks after vaccination with the ChAdOx1-S (AstraZeneca) vaccine. Both patients were asymptomatic prior to vaccination and PCR of nasopharyngeal swab for SARS-CoV-2 and other respiratory viruses associated with SAT was negative. Serology testing for measles, mumps, rubella, CMV and EBV viruses was suggestive of immunity. Antibody titre against spike S protein of SARS-CoV-2 was measured for both patients and was indicative of adequate post vaccination antibody response. Two months after initial assessment, both patients were euthyroid and asymptomatic. Subacute as well as silent thyroiditis may rarely occur after vaccination against COVID-19. Further research is needed to investigate the prevalence and pathogenesis of thyroid dysfunction following vaccination against COVID-19.


Molecular genetic basis of primary inherited optic neuropathies.
To review the molecular genetic basis of primary inherited optic neuropathies. Medline and Embase search. Inherited optic neuropathies are a genetically diverse group of disorders that present with reduced visual acuity and the clinical appearance of optic atrophy. The inherited optic neuropathies may be sporadic or familial, in which case the mode of inheritance may be Mendelian (autosomal dominant, autosomal recessive, X-linked recessive) or non-Mendelian (mitochondrial). Two genes for dominantly inherited optic atrophy have been mapped (OPA1 and OPA4), of which the gene has been identified in one (OPA1). A gene for recessive optic atrophy (OPA3) has also been identified. X-linked optic atrophy (OPA2) has been mapped but to date no gene has been identified. Mutations in mitochondrial DNA have been identified in Leber's hereditary optic neuropathy. Mutations in genes from both the nuclear and mitochondrial genomes appear to be responsible. Mitochondrial dysfunction, in the broadest sense, is emerging as central to the pathogenesis of this group of conditions.


Cognition and brain health among older adults in Iceland: the AGES-Reykjavik study.
The paper aimed to compare how factors previously identified as predictive factors for cognitive decline and dementia related to cognitive performance on the one hand and brain health on the other. To that aim, multiple linear regression was applied to the AGES-Reykjavik study epidemiological data. Additionally, a regression analysis was performed for change in cognition over 5 years, using the same exposure factors. The study ran from 2002 to 2011, and the sample analyzed included 1707 participants between the ages of 66 and 90. The data contains MR imaging, cognitive testing, background data, and physiological measurements. Overall, we conclude that risk factors linked to dementia relate differently to cognition and brain health. Mobility, physical strength, alcohol consumption, coronary artery disease, and hypertension were associated with cognition and brain volume. Smoking, depression, diabetes, and body fat percentage were only associated with brain volume, not cognitive performance. Modifiable factors previously linked to cognitive reserve, such as educational attainment, participation in leisure activities, multilingualism and good self-reported health, were associated with cognitive function but did not relate to brain volume. These findings show that, within the same participant pool, cognitive reserve proxy variables have a relationship with cognitive performance but have no association with relative brain volume measured simultaneously.


Psychiatric disorders in primary focal dystonia and in Parkinson's disease.
Primary focal dystonia and Parkinson's disease are movement disorders that have contrasting motor phenotypes. The aim of this study was to compare the frequency and the severity of psychiatric disorders in primary focal dystonia and Parkinson's disease. Two groups of 30 patients matched by gender and age underwent a neurological and psychiatric assessment. Parkinson's disease patients were diagnosed with higher rates of major depression (P = 0.02) and generalized anxiety disorder (P = 0.02), and greater severity of depressive symptoms (P = 0.04), while patients with primary focal dystonia exhibited increased severity of obsessive-compulsive symptoms (P = 0.02). The difference in pathophysiology of primary focal dystonia and Parkinson's disease may explain the different psychiatric profiles of these two diseases. The increased frequency of affective symptoms in Parkinson's disease may be related to the fact that Parkinson's disease is a neurodegenerative disease marked by the loss of monoaminergic neurons which does not happen in primary focal dystonia. The psychiatric profile differs in movement disorders with distinct neurobiological bases.


A scale for assessing quality of life in adult asthma sufferers.
The Asthma Questionnaire is a 68-item quality of life scale designed to be sensitive to quality of life changes in clinical trials. The questionnaire covers 11 domains of life experience, the initial domain and item sets being derived from six qualitative focus groups of asthma patients. Psychometric analysis of responses of 101 asthma patients to the initial 101-item set showed the scale to be unidimensional despite being multi-domain, and the finding of unidimensionality was replicated during the further three stages of item refinement using 783 patients. The scale compensates for acquiescence bias as well as allowing a 'not applicable' response category. Validity of the scale was demonstrated by confirmation of expected group differences and the retest reliability was 0.948.


[Biosynthetis in vitro of estrogens by an adrenal cortex tumor].
A polysecretory cortico-adrenal tumor from a 46 year old woman was incubated in presence of tritiated pregnenolone and progesterone. Nine estrogens were isolated and identified by radio-gas-chromatography. This outstanding synthesis ability was in line with the high rates of urinary estrogens found in this patient.


Eosinophilic cystitis induced by mitomycin-C.
Eosinophilic cystitis is an unusual form of cystitis which is characterized by irritative voiding symptoms and haematuria. In the report herein two adult cases of eosinophilic cystitis treated with intravesical Mitomycin-C instillations for prophylaxis of bladder carcinoma are presented and the literature is reviewed.


Proteins and renal fibrosis: low-protein diets induce Kruppel-like factor-15, limiting renal fibrosis.
The mechanisms underlying beneficial influences of low-protein diets on the progressive nature of chronic kidney disease are incompletely understood. Gao et al. identify a downregulation of Kruppel-like factor-15 (KLF15) associated with increased renal fibrosis. The KLF15 downregulation and renal fibrosis are reversed with dietary protein restriction, especially when ketoacids are added. The results suggest that KLF15 may play a role in suppressing renal fibrosis and could contribute to the benefits of dietary protein restriction.


[Diagnostic markers in urology].
Cancer diagnostics can be supplemented by disease-related biomarkers. In the course of modern patient-tailored cancer treatment, the importance of correct risk stratification, prognosis and monitoring has significantly increased. In recent years, a multitude of biomarkers and related test procedures have emerged to fulfil this purpose. The following review article summarizes the most recent developments with respect to the use of biomarkers in the diagnostics of urological cancers.


Inactivation of potent pyrolysate mutagens by chlorinated tap water.
The potent mutagens 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2, 62450-07-1), 2-amino-6-methyldipyrido-[1,2-a:3', 2'-d]imidazole (Glu-P-1, 67730-11-4) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 76180-96-6), isolated from pyrolysates of tryptophan and glutamic acid and from broiled sardines, respectively, were effectively degraded by chlorinated tap water with a concomitant loss of mutagenicity toward Salmonella typhimurium TA98 and TA100. The half-life of 10 microM IQ in the presence of 1.5 ppm of residual chlorine was less than 10 sec; those of Glu-P-1 and Trp-P-2 were 0.5-1 and 2-3 min, respectively. This means that a glass of chlorinated tap water (150 ml) containing 1.5 ppm of residual chlorine can break down about 200 micrograms of these pyrolysate mutagens within a couple of minutes.


Inhibition effects of perfluoroalkyl acids on progesterone production in mLTC-1.
Perfluoroalkyl substances (PFASs) are a class of fluorine substituted carboxylic acid, sulfonic acid and alcohol, structurally similar to their corresponding parent compounds. Previous study demonstrated the potential endocrine disruption and reproductive toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid, two dominant PFASs in animals and humans. We explored the relationship between eleven perfluoroalkyl acids (PFAAs) with different carbon chain length and their ability to inhibit progesterone production in mouse Leydig tumor cells (mLTC-1). We found an obvious dose-response relationship between progesterone inhibition rate and PFAA exposure concentration in mLTC-1. The relative inhibition rate of progesterone by PFAAs was linearly related to the carbon chain length and molar refractivity of PFAAs. Mitochondrial membrane potential (MMP) decreased after PFAA exposure at the half-maximal inhibitory effect concentration (IC50) of progesterone production in mLTC-1, while the reactive oxygen species (ROS) content increased significantly. These results imply that the inhibition effect of PFAAs on progesterone production might be due, in part, to ROS damage and the decrease in MMP in mLTC-1.


Zinc supplementation during pregnancy: a double blind randomised controlled trial.
To see whether zinc supplementation during pregnancy improves maternal and fetal outcome. Prospective study started at booking and continued till discharge of mother and baby from the maternity hospital. Mothers were randomly assigned to receive zinc supplementation or placebo in a double blind trial. Mothers booking at one hospital. Women booking before 20 weeks of gestation who agreed to take part in the study. 494 Mothers were followed up till the end of pregnancy. There was no difference between the groups given zinc and placebo in their social or medical backgrounds. Mothers in the active treatment group received one capsule of 20 mg elemental zinc daily and those in the placebo treated group a capsule identical in appearance and taste with the active capsule but which contained inert substances. Various adverse outcomes were tested, including maternal bleeding, hypertension, complications of labour and delivery, gestational age, Apgar scores, and neonatal abnormalities. The main outcome measure was birth weight. There were no differences whatsoever between mothers given a zinc supplement and those given a placebo. Zinc supplementation in pregnancy in the United Kingdom does not seem to offer any benefits to the mother or her fetus.


The use of 29 MHz transrectal micro-ultrasound to stratify the prostate cancer risk in patients with PI-RADS III lesions at multiparametric MRI: A single institutional analysis.
Magnetic Resonance Imaging (MRI) has emerged as the most accurate diagnostic tool, showing a high sensitivity in the diagnosis of clinically significant prostate cancer (csCaP). However only a minority of patients with a PI-RADS 3 lesion at multiparametric magnetic resonance imaging (MRI) are diagnosed with csCaP. The aim of the current study was to assess whether high resolution micro-ultrasound (microUS) could help in sub-stratifying the risk of csCaP in this specific population. We retrospectively analyzed the records of 111 consecutive patients scheduled for a prostate biopsy with at least 1 PI-RADS 3 lesions at MRI. We excluded patients with a PIRADS >3 lesion, even if they had a coexisting PIRADS 3 lesions. MicroUS was performed in all patients before prostate biopsy by an operator blind to MRI results. The Prostate Risk Identification using MicroUS (PRI-MUS) protocol was used to assess the risk of CaP and csCaP. All patients received both targeted and systematic biopsies. The primary endpoint was to determine the diagnostic accuracy of microUS in detection of csCaP in patients with a PI-RADS 3 lesion at MRI. Specifically, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of microUS were determined. Multivariable logistic regression models (MLRMs) were fitted to identify predictors of CaP. The diagnostic accuracy was reported as area under the receiver operator characteristic (ROC) curve. Overall, 43 patients (38.7%) harboured CaP and 22 (20%) csCaP. MicroUS showed a high sensitivity and negative predictive value (100%), while its specificity and positive predictive value were 33.7% and 27.2%, respectively. Among patients without lesions at microUS, 25 (83.3%) did not harbour CaP, while 5 (16.7%) patients were diagnosed with a Gleason score 6 CaP, with no patients harbouring csCaP. Using microUS, the csCaP detection would have remained 100%, while reducing the detection of insignificant CaP of a 23.8% extent (n = 5). In MLRMs, lesion identified at microUS and continuously-coded PSAd were independent predictors of CaP. The accuracy of a model including PRI-MUS score, digital rectal examination (DRE), PSA density, age and family history was 0.744 (95% CI: 0.645 - 0.843). In our single-institutional retrospective study, microUS was potentially capable to stratify the presence of CaP in patients with an equivocal MRI. Further prospective studies on larger populations are needed to validate our results.


Spinal Versus General Anesthesia for Lumbar Decompression or Sequestrectomy in Patients Over 75 Years.
Decompression or sequestrectomy in the lumbar spine can be performed under general (GA) or regional anesthesia. In elderly patients, it is still not clear, which procedure should be chosen. To demonstrate that spinal anesthesia (SA) is a safe choice for lumbar decompression or sequestrectomy in elderly patients. Retrospective clinical single-center study. We included 154 patients with ages over 75 years after lumbar decompression or sequestrectomy. The mean age of the patients was 81 years. Perioperative data (blood loss, dural tear, operative and perioperative time, delirium, urinary retention, and hospital stay) and the postoperative 1-year follow-up (visual analog scale and complication rate). Data were retrospectively collected from patients that underwent lumbar decompression or sequestrectomy between January 2019 and December 2020. The data from the GA and SA groups were compared. SA was performed in 56 patients whereas 98 patients received a GA. There was no clinically relevant difference between both groups with comparable complication rates. The time of surgery, blood loss, perioperative time, and hospital stay time were significantly less in the SA group. SA and GA are both safe and reliable procedures for lumbar decompression or sequestrectomy in elderly patients with no clinically relevant difference.


Interference with a conformational change in the haemagglutinin molecule of influenza virus by antibodies as a possible neutralization mechanism.
A possible mechanism of neutralization of influenza virus by antibodies to the haemagglutinin molecule is proposed in addition to the generally accepted mechanism of blocking attachment to host cell receptors. This proposed mechanism involves interference with a low-pH-induced conformational change in the haemagglutinin molecule by bivalent binding of antibodies, which results in inhibition of the fusion step in the viral replication process.


Ventilatory response to CO2 with Read's rebreathing method in normal infants.
Methods of evaluating the ventilatory response to CO2 (VRCO2 ) of the respiratory center include the steady-state and the rebreathing method. Although the rebreathing method can evaluate the ventilatory response continuously to gradually increasing CO2 , the rebreathing method has been rarely performed in infants. The aim of this study was to investigate whether we could perform the VRCO2 with the rebreathing method in normal infants. The subjects were 80 normal infants. The gestational age was 39.9 (39.3-40.3) weeks, and the birth body weight was 3142 (2851-3451) grams. We performed the VRCO2 with Read's rebreathing method, measuring the increase in minute volume (MV) in response to the increase in EtCO2 by rebreathing a closed circuit. The value of VRCO2 was calculated as follow: VRCO2 (ml/min/mmHg/kg) = ΔMV/ΔEtCO2 /body weight. We performed the examination without adverse events. The age in days at examination was 3 (2-4), and the examination time was 150 ± 38 s. The maximum EtCO2 was 51.1 (50.5-51.9) mmHg. The value of VRCO2 was 34.6 (29.3-42.8). The intraclass correlation coefficient of the VRCO2 of cases with multiple measurements was 0.79. This study suggests that the rebreathing method can evaluate the ventilatory response to high blood CO2 in a short examination time. We conclude that the rebreathing method is useful even in infants. In the future, we plan to measure the VRCO2 of preterm infants, and evaluate the respiratory center of infants in more detail.


Withdrawal notice to: <Describing the unvaccinated as the main driver of the current COVID-19 situation in Germany should not be based on analyzing pre-pandemic patterns of contacts> <[The Lancet Regional Health Europe 12 (2022) 100290]>.
[This retracts the article DOI: 10.1016/j.lanepe.2021.100290.].


Animal model estimation of non-additive genetic parameters in dairy cattle, and their effect on heritability estimation and breeding value prediction.
First lactation production records of pedigree Holstein-Friesian cows in the UK were analysed by an animal model, in order to estimate effects of heterosis and recombination loss between North American Holstein and European Friesian cattle and the influence of these effects on breeding value prediction. Coefficients of heterosis and recombination loss were fitted in the animal model as covariables and unknown parents were assigned to a varying number of genetic groups. The estimates of heterosis effects were 104 kg, 4.3 kg and 2.9 kg for milk, fat and protein yield, respectively, while the corresponding coefficients for recombination loss were -135 kg, -2.6 kg and -3.7 kg respectively. Neither the sire component of variance nor the heritability estimates were appreciably affected by the inclusion of heterosis and recombination loss in the model. Including both these effects in the breeding value estimation increased the predicted sire proof for fat plus protein of a typical F1 Holstein × Friesian sire by 3 kg. ZUSAMMENFASSUNG: Tiermodellschätzungen nicht-additiv genetischer Parameter bei Milchrindern und ihre Auswirkung auf Heritabilitätsschätzung und Zuchtwertvoraussage Laktationsleistungen von Herdbuch Holstein-Friesen Kühen im UK wurden mittels eines Tiermodells analysiert zur Schätzung der Wirkungen von Heterosis und Rekombinationsverlust zwischen nordamerikanischen Holstein und europäischen Schwarzbunten und Einfluß dieser Wirkungen auf Zuchtwahlvorhersagen. Koeffizienten für Heterosis und für Rekombinationsverlust wurden im Tiermodell als Co-Variable berücksichtigt und unbekannte Eltern einer unterschiedlichen Zahl genetischer Gruppen zugeordnet. Schätzungen der Heterosiswirkungen waren 104 kg, 4,3 kg und 2,1 kg für Milch-, Fett- Proteinmengen, während die diesbezüglichen Koeffizienten für Rekombinationsverlust -135, -2,6 und -3,7 kg waren. Weder die Vatervarianzkomponente noch Heritabilitätswerte wurden durch Berücksichtigung von Heterosis und Rekombinationsverluste im Modell tangiert. Berücksichtigung beider Wirkungen in der Zuchtwertschätzung erhöhte den geschätzten Vaterzuchtwert für Fett + Protein eines typischen F1 Holstein-Friesen-Stieres um 3kg.


Microclimate exerts greater control over litter decomposition and enzyme activity than litter quality in an alpine forest-tundra ecotone.
Plant litter decomposition is an important biogeochemical process in terrestrial ecosystems. Although climate and substrate quality controls over litter decomposition are reasonably well understood, their impacts on lignocellulose degradation and lignocellulolytic enzymes remain elusive. Here, the decomposition of three leaf litters derived from Salix paraplesia (SP), Deyeuxia scabrescens (DS), and Ajuga ovalifolia (AO), was studied across an alpine forest-tundra ecotone during one snow-covered season with the objective of distinguishing between the effects of microclimate and litter quality on litter decomposition rates and lignocellulolytic enzymes. The results showed that both microclimate and litter quality affected lignocellulose degradation rates and lignocellulolytic enzyme activities; however, microclimate factors had the greater effects. Interestingly, freeze-thaw cycles and moisture were the predominant factors explaining the variations in decomposition rate and enzyme activities. Higher cellulose degradation rates were associated with higher cellulose concentrations. Cellulolytic enzymes had a greater effect on litter decomposition than did ligninolytic enzymes at the early decomposition stage. Litter decomposition and enzyme activities should be given more attention under global climate change, as the direction and magnitude of changes in microclimate factors and litter quality could strongly influence the nutrient cycling and energy fluxes of alpine ecosystems.


Visualization of epidermal growth factor (EGF) receptor aggregation in plasma membranes by fluorescence resonance energy transfer. Correlation of receptor activation with aggregation.
Fluorescence resonance energy transfer between epidermal growth factor (EGF) molecules, labeled with fluorescent reporter groups, was used as a monitor for EGF receptor-receptor interactions in plasma membranes isolated from human epidermoid A431 cells. Epidermal growth factor molecules labeled at the amino terminus with fluorescein isothiocyanate served as donor molecules in these energy transfer measurements, while EGF molecules labeled with eosin isothiocyanate at the amino terminus served as the energy acceptors. Both of these derivatives were shown to be active in binding to membrane receptors and in the activation of the endogenous receptor/tyrosine kinase activity. We found that membranes in the absence of added metal ion activators showed relatively little energy transfer (approximately 10% donor quenching) between the labeled growth factors. However, divalent metal ion activators of the EGF receptor/tyrosine kinase caused a significant increase in the extent of energy transfer between the labeled EGF molecules. Specifically, in the presence of 20 mM MgCl2, the extent of quenching of the donor fluorescence increased to 25% (from 10% in the absence of metal), while in the presence of 4 mM MnCl2, the extent of energy transfer was increased still further to 40-50%. The addition of an excess of EDTA resulted in the reversal of the observed energy transfer to basal levels. The increased energy transfer in the presence of these divalent cations correlated well with the ability of these metals to stimulate the EGF receptor/tyrosine kinase activity. However, the extent of receptor-receptor interactions measured by energy transfer was independent of receptor autophosphorylation. Overall, these results suggest that conditions under which the EGF receptor is primed to be active as a tyrosine kinase, within a lipid milieu, result in an increased aggregation of the receptor.


The effect of prednisolone and ketotifen on the antigen-induced bronchoconstriction and mediator release in rat isolated lungs.
Using a new method for inducing IgE-mediated, systemic anaphylaxis in the rat both prednisolone and ketotifen had been shown previously to be effective in suppressing the bronchial anaphylaxis in vivo. In order to study the mode of action underlying their bronchoprotective effect, both agents were also tested on the antigen-induced bronchoconstriction in rat isolated lungs in relation to the mediator release in the lung-effluent. The presence of histamine, 5-hydroxytryptamine (5-HT) and SRS-A could be detected biologically in the lung-effluent during bronchoconstriction. Histamine and 5-HT were determined quantitatively by means of h.p.l.c. with fluorimetric detection, whereas SRS-A was determined using the guinea-pig ileum in a cascade set-up. Although both prednisolone and ketotifen inhibited the antigen-induced bronchoconstriction effectively, it appeared that only prednisolone suppressed the release of histamine, 5-HT and SRS-A in the lung-effluent significantly, whereas ketotifen had no effect. On account of these data it is suggested that the bronchoprotective effect of prednisolone is mainly based on inhibition of the release of the mediators involved, whereas the effect of ketotifen may be based on receptor antagonism.


Special Issue: Recombinant Protein Expression in Microorganisms.
Microorganisms are widely used in industrial biotechnology as cell factories for the sustainable production of a wide range of compounds and chemicals [...].


Effects of Diets Containing Finger Millet Straw and Corn Straw on Growth Performance, Plasma Metabolites, Immune Capacity, and Carcass Traits in Fattening Lambs.
As the byproduct of finger millet, millet straw is a new forage resource of ruminants. The effect of the combined utilization of millet straw with corn straw on fattening lamb production is seldom reported. The purpose of this study was to investigate the effect of different proportions of millet straw instead of corn straw on the growth performance, blood metabolites, immune response, meat yield, and quality of fattening lamb. Sixty-three-month-old healthy Small-Tailed Han sheep crossbred rams with an average initial weight of 19.28 ± 2.95 kg were randomly divided into four groups, with three replicates in each group and five lambs in each replicate. The replacement ratio of millet straw of each group (Group I, II, III, IV) was 0%, 25%, 35%, 50% at the first stage (the first two months) and 0%, 20%, 28%, 40% in the second period (final two months), respectively. The experiment lasted 4 months 10 days of the pre-feeding period. The results indicated that the body weight gain and average daily gain of group Ⅱ were significantly higher than those of group Ⅰ and group Ⅳ (p < 0.05). The concentration of total protein in group Ⅳ was significantly increased compared to those of the other three groups at the second stage (p < 0.05), which proved that the protein synthesis metabolism capacity was improved with the addition of millet straw. The concentration of the plasma glutamic-oxalacetic transaminase and lactic dehydrogenase of lambs was significantly decreased in group Ⅱ (p < 0.05). The combination of millet straw and corn straw had no impact on the glucose, total cholesterol, and triglycerides metabolism (p > 0.05). There was no significant difference in the pre-slaughter weight, carcass weight, dressing percentage, loin-eye area, and GR value among the four groups (p > 0.05). Furthermore, the immune response and meat quality were not impacted by the different proportions of millet and corn forage diets. The results showed that the combined utilization of millet straw with corn straw could improve the blood biochemistry metabolism capability of fattening lambs. The replacement of 50% of corn straw with millet straw could improve the growth performance and be an application in fattening lamb production.