Management of COVID-19 ICU-survivors in primary care: - a narrative review.

Many survivors of critical illness suffer from long-lasting physical, cognitive, and mental health sequelae. The number of affected patients is expected to markedly increase due to the COVID-19 pandemic. Many ICU survivors receive long-term care from a primary care physician. Hence, awareness and appropriate management of these sequelae is crucial. An interdisciplinary authorship team participated in a narrative literature review to identify key issues in managing COVID-19 ICU-survivors in primary care. The aim of this perspective paper is to synthesize important literature to understand and manage sequelae of critical illness due to COVID-19 in the primary care setting.

Local and Nonlocal Electron Dynamics of Au/Fe/MgO(001) Heterostructures Analyzed by Time-Resolved Two-Photon Photoemission Spectroscopy.

Employing femtosecond laser pulses in front and back side pumping of Au/Fe/MgO(001) combined with detection in two-photon photoelectron emission spectroscopy, we analyze local relaxation dynamics of excited electrons in buried Fe, injection into Au across the Fe-Au interface, and electron transport across the Au layer at 0.6 to 2.0 eV above the Fermi energy. By analysis as a function of Au film thickness we obtain the electron lifetimes of bulk Au and Fe and distinguish the relaxation in the heterostructure's constituents. We also show that the excited electrons propagate through Au in a superdiffusive regime and conclude further that electron injection across the epitaxial interface proceeds ballistically by electron wave packet propagation.

[Psychological treatments for pain in cancer patients : A systematic review on the current state of research]. / Schmerzpsychologische Interventionen bei onkologischen Patienten : Ein systematisches Review zum aktuellen Stand der Forschung.

BACKGROUND: In cancer patients, pain is one of the main symptoms and especially in the late stages of disease, these symptoms can be associated with considerable suffering. In psycho-oncology, preliminary psychological therapies targeting cancer pain have been tested; however, a systematic review of available interventions is lacking, especially considering their dissemination, evidence base, study quality, and the comparison with established treatments. Therefore, the aim of the current study is to systematically review the current research on psychological treatments for pain in cancer patients. MATERIALS AND METHODS: During May 2014, MEDLINE, PsycINFO, PSYNDEX, and CENTRAL databases were searched. Psychological treatments for pain in adult cancer patients studied in randomized, controlled trials (RCTs) and referring to pain as primary or secondary outcome were included. After examination for inclusion, structured data extraction and assessment followed. Data were synthesized narratively. RESULTS: In the review, 32 RCTs were included. Studies mainly referred to patients with breast cancer or patients in earlier stages of the disease. The methodological quality of included studies was heterogeneous. Most commonly, short interventions were delivered by nurses in out-patient settings. Interventions including education and relaxation techniques were utilized most often, followed by interventions with behavioral or cognitive components. CONCLUSION: A need for research persists regarding efficacy of current psychotherapeutic interventions, or the role of mediator variables (e. g., coping) on pain perception in cancer patients. Studies with high methodological quality which comprehensively and transparently report on interventions and designs are lacking.

Inhibition of the heme-induced hemolysis of red blood cells by thechlorite-based drug WF10.

Excessive release of hemoglobin from red blood cells markedly disturbs the health status of patients due to cytotoxic effects of free hemoglobin and heme. The latter component is able to initiate novel hemolytic events in unperturbed red blood cells. We modeled this process by incubation of ferric protoporphyrin IX with freshly isolated red blood cells from healthy volunteers. The heme-induced hemolysis was inhibited in a concentration-dependent manner by the chlorite-based drug WF10, whereby the hemolysis degree was totally abolished at a molar ratio of 1:2 between chlorite and heme. Upon incubation of heme with WF10, the ultraviolet-visible spectrum changed, whereas the release of iron from heme and the appearance of fluorescent breakdown products of the porphyrin ring were negligible at this ratio, but increased with increasing excess of chlorite over heme. Thus, inhibition of hemolysis by WF10 takes already place at those chlorite concentrations, where no degradation of the porphyrin ring occurs. As WF10 is applied in form of an intravenous infusion to patients with severe inflammatory states, these data support the hypothesis that the beneficial WF10 effects are closely associated with inactivation of free heme.

[Causes, diagnosis, and animal behavioural therapy of feline house soiling]. / Ursachen, Diagnose und verhaltensmedizinische Therapie der Unsauberkeit von Katzen.

Feline house soiling, i. e. urinating or defecating outside the litterbox, is the most common behavioural problem for which cat owners seek assistance from veterinarians. The reasons for feline house soiling are inappropriate toileting or urine marking. To identify the initiating cause(s) and maintaining factors, a comprehensive behavioural history is required. Urine marking may be caused by anxiety-evoking stuations or arousing events, whereas inappropriate toileting is mainly due to factors related to the litterbox. The treatment plan should initially focus on the pet's well-being. Therefore, it is important to improve the litterbox management to curtail the problem. The main approaches to resolve feline house soiling involve avoiding the cat's exposure to triggering stimuli, re-establishing regular litterbox use, and behavioural modification.

The discriminatory capacity of BMD measurements by DXA and dual X-ray and laser (DXL) at the calcaneus including clinical risk factors for detecting patients with vertebral fractures.

UNLABELLED: Osteoporotic fracture risk depends on bone mineral density (BMD) and clinical risk factors (CRF). Five hundred and eighty-eight untreated female and male outpatient subjects were evaluated, 160 with vertebral fractures. BMD was measured both by using calcaneal dual X-ray and laser (DXL) and dual-energy X-ray absorptiometry (DXA), and CRF were evaluated. Detection frequencies for different BMD methods with or without CRF are presented. INTRODUCTION: Osteoporotic fracture risk depends on bone mineral density and clinical risk factors. DXA of the spine/hip is considered a gold standard for BMD assessment, but due to degenerative conditions, particularly among the older population, assessment of BMD at the lumbar spine has been shown to be of limited significance. Portable calcaneal dual X-ray technology and laser can be an easily obtainable alternative. METHODS: Vertebral fractures were evaluated in a baseline analysis of 588 females and males (median age 64.4, range 17.6-93.1 years), comparing BMD measurements by using DXL and DXA and CRF with/without BMD. One hundred and sixty subjects had radiological verified vertebral fractures. Area under receiver-operating characteristic curves (AUROCC) and univariate and multiple logistic regressions were calculated. RESULTS: AUROCC for detection of vertebral fractures was comparable for DXL at calcaneus and DXA at femoral neck (DXL 0.665 and DXA 0.670). Odds ratio for prevalent vertebral fracture was generally weak for DXA femoral neck (0.613) and DXL (0.521). Univariate logistic regression among CRF without BMD revealed age, prevalent fragility fracture, and body mass index significantly associated with prevalent vertebral fracture (AUROCC = 0.805). Combining BMD and CRF, a prognostic improvement in case of DXA at femoral neck (AUROCC 0.869, p = 0.02), DXL at calcaneus (AUROCC 0.869, p = 0.059), and DXA at total hip (AUROCC 0.861, p = 0.06) was observed. CONCLUSIONS: DXL was similarly sensitive compared with DXA for identification of subjects with vertebral fragility fractures, and combination of CRF with BMD by DXL or DXA further increased the discriminatory capacity for detection of patients susceptible to vertebral fracture.

[Castration of dogs from the standpoint of behaviour therapy]. / Kastration von Hunden aus Sicht der Tierverhaltenstherapie.

The castration of dogs is an amputation covered by Section 6 (1) of the Animal Protection Law in Germany. Apart from the general indications given by veterinary medicine, castration of an animal is a potential method of animal behaviour therapy. However, the highly variable, individual effects of castration on behaviour require detailed diagnosis by the veterinarian. Castration appears to exert its strongest influence on sexually dimorphic behaviour patterns in male dogs, e.g. status- related aggression, urine marking, mounting, house-soiling problems, and roaming. An indication to castrate a bitch is maternal aggression. When evaluating the effects of castration, one should always consider individual circumstances, such as learning experience (for example in the case of "experienced copulators"), age, and pack behaviour (if there is more than one dog in the household). Additional benefits of castration include a reduction in the dog's general activity level, decreased preparatory arousal and a decline in the dog's ability to focus its attention fully on the target of attack. As a result, it is much easier for the owner to disrupt and manage or control the dog's agonistic intentions. However, castration is not the ultimate remedy in dog-handling. Any decision in this respect should be based on a precise behaviour- related indication. Otherwise, such surgery may well violate the Animal Protection Law.

Redirected behavior in learning tasks: the commercial laying hen (Gallus gallus domesticus) as model.

Redirected behaviors occur when some course of action is thwarted or inhibited (frustration). They also occur as adjunctive behaviors in operant conditioning tasks, where they might reflect frustration about unrewarded responses. Because frustration is associated with stress, which could interfere with learning and memory, we studied whether the occurrence of redirected behavior is correlated with learning success in a series of visual-cue discrimination tasks. Eleven hens, aged 34 wk, were tested on acquisition, reversal, extinction, and relearning of a simple visual discrimination task. The experimenters randomly assigned red and blue cardboard discs as discriminative stimuli. A correct response was recorded when a hen pecked at the correct disc. The learning criterion was 90% correct responses in 20 trials in 2 consecutive task sessions. The following data were documented: number of pecks needed to achieve the learning criterion, latency in choosing, pecks at the experimenter, and pecks at the surroundings. The behavioral responses were analyzed using linear mixed model ANOVA. Redirected pecking at the surroundings was a significant indicator of learning failure in that the more the hens performed this behavior, the more trials they needed to complete the discrimination tasks (P = 0.012). The number of pecks at the experimenter during the tasks significantly influenced learning success (P = 0.020), with hens directing more pecks at the experimenter during reversal, reaching the learning criterion in fewer trials (P = 0.027). The more the hens pecked at the experimenter during acquisition and extinction, however, the more trials they needed to meet the learning criteria (acquisition: P = 0.048; extinction: P = 0.003). Thus, laying hens are susceptible to the effects of frustration as measured in terms of redirected pecking elicited by operant procedures in visual discrimination tasks. In general, any situation in which a desirable goal is obstructed or an expected reward is omitted may lead to frustration-related activities, such as redirected behavior, which could in turn lead to abnormal behavior and welfare issues for the animals.

[Specialized outpatient palliative care. The expectations of general practitioners]. / Spezialisierte ambulante Palliativversorgung. Die Erwartungen von Hausärzten.

BACKGROUND: The aim was to explore the expectations of general practitioners (GPs) towards specialized outpatient palliative care (SAPV) focused on older patients in the last phase of life. METHODS: A standardized postal survey was carried out with 1,962 GPs in Lower Saxony with an analysis of physician and practice-related factors. RESULTS: The response rate was 46% (n=897) and SAPV was known to 68% of the participants (n=599) of whom 48% (n=288) assumed that SAPV will improve the healthcare for older patients in the last phase of life. The GPs favored advice by and collaborative patient care with SAPV teams. Younger and female GPs, and GPs who had been practicing for a shorter period or working in a group practice showed greater interest in collaboration than other colleagues. CONCLUSIONS: The perception of patients in specialized palliative care with its current focus on cancer patients is different from the perception in general practice with its focus on geriatric and multimorbid patients. This may be a reason for the skepticism showed in this study whether SAPV will actually improve healthcare in the community. However, with respect to the concept and framework SAPV has the potential to fulfill GPs expectations and should be focused on counseling and collaborative services. The knowledge about physician and practice-related factors shaping GPs attitudes towards SAPV can be helpful to further implement SAPV into practice.

Oestrogen imprinting causes nuclear changes in epithelial cells and overall inhibition of gene transcription and protein synthesis in rat ventral prostate.

Oestrogen exposure during the early post-natal period affects male growth, physiology, and susceptibility to disease in adult life. The prostate gland is susceptible to this oestrogen imprinting, showing a reduced expression of the androgen receptor and inability to respond to androgen stimulus. In this context, we decided to study key signalling regulators of ventral prostate (VP) functioning after early postnatal exposure to high-dose oestrogen. Our results showed a decrease of mTOR phosphorylation and its direct downstream target 4EBP. It is known that mTOR-induced signalling is a pivotal pathway of cell metabolism, which is able to control gene transcription and protein synthesis. We then decided to investigate other indicators of a reduced metabolism in the oestrogenized prostate, and found that the luminal epithelial cells were shorter, less polarized and had smaller nuclei containing more compacted chromatin, suggesting that a general mechanism of regulating gene expression and protein synthesis could be installed in the epithelium of the oestrogenized VP. To evaluate this idea, we analysed nucleolar morphology, and measured the amount of ribosomes and the level of methylation of the 45S ribosomal RNA promoter region. These data indicated that the nucleolus was dismantled and that the methylation at the 45S promoter was increased ( approximately five-fold). Taken together, the results support the idea that the oestrogenized prostate maintains a very low transcriptional level and protein turnover by affecting canonical signalling pathways and promoting nuclear and nucleolar changes.

[Current vaccination status of health-care personnel in Brandenburg, Saxony And Saxony-Anhalt]. / Aktueller Impfstatus in unterschiedlichen medizinischen Berufsgruppen in Brandenburg, Sachsen und Sachsen-Anhalt.

OBJECTIVE AND METHODS: A complete vaccination status against infectious diseases is important for protecting health care professionals as well as patients. A survey based on a written questionnaire was conducted to record the actual vaccination status against diphtheria, hepatitis A und B, mumps, measles, poliomyelitis, rubella and tetanus. 642 general practitioners (family physicians and surgeons), 298 medical students and 962 nursing students from areas of eastern Germany completed the questionnaire. RESULTS AND CONCLUSIONS: There was no complete vaccination status against those diseases covered by the survey. Physicians had a good immunisation rate against tetanus (96.2%) and diphtheria (91.8%). The number of physicians without immunisation against measles (42.9%), HA (29.3%) and HB (12.7%) was unsatisfactory. Less than 50% of nursing students and medical students could show a complete vaccination status against MMR. In both student groups there were also gaps for vaccines against tetanus, diphtheria, HA and HB. Complete vaccination status was found to be in the range of 74-81% for tetanus, 51-66% for diphtheria, 47-63% for HA and 62-73% for HB. Furthermore, there is a need for actions to raise the immunisation rates and for improving the health protection for all persons involved (professionals and patients) in the health care system.

[Animal welfare legal aspects of rodeo events]. / Tierschutzrechtliche Aspekte bei Rodeo-veranstaltungen.

Rodeo events have been criticised by animal welfare organisations as being adverse to animal protection, for years. This was the motive for TVT to put several of these criticised disciplines to evaluation in terms of animal protection aspects. For that purpose, various rodeo events were visited, and videotaped material of almost all events, which had taken place in Germany in 2003 and 2004, was evaluated. Rodeo events are subject to and 11, sec.1, No. 3d, German Animal Protection Act, which implies compulsory accreditation. In the scope of such events, causing any sort of pain and suffering (and 3 No. 6 German Animal Protection Act) is prohibited. A proof of the severity of the pain caused, is therefore no necessity. For the "critical" disciplines "Bare Back Riding" and "Saddle Bronc Riding" a so called "flank" is used. A flank is a leather strap, fastened to the sensitive parts of the horse skin, (around the flanks,) which is tightened to a maximum as soon as the horse is released from the starting box. Analysis show, that the strap has to be seen as the trigger for the wanted kow-tow. The different coping strategies shown by the animals prove that the leather strap is an apt instrument to cause pain and/or suffering (anxiety/fear/stress) in horses. Bull riding, instead, showed that the rider has to be seen primarily as the trigger for defence behaviour, here. In consideration of the current legal position and taking ethic principles into account, it seems appropriate to only authorise rodeo events under the condition of a flank strap ban. Bull riding should be banned in general.

Association between uncoupling protein 3 gene and obesity-related phenotypes in the Québec Family Study.

BACKGROUND: UCP3 is a mitochondrial membrane transporter that is postulated to uncouple oxidative phosphorylation from ATP synthesis producing heat instead of ATP. Human UCP3 is mainly expressed in skeletal muscle, which plays an important role in energy homeostasis and substrate oxidation. Therefore, UCP3 is a good candidate gene for obesity. MATERIALS AND METHODS: We analyzed, among 734 subjects from the Québec Family Study, a new GA repeat microsatellite located in intervening sequence (IVS) 6 (GAIVS6) in UCP3 gene, and two already described restriction fragment length polymorphisms (RFLP) Y210Y(C-->T) and V102I(G-->A). Covariance analysis across genotypes for different adiposity, resting energy expenditure, and glucose metabolism variables was undertaken with age and sex, plus body fat and body mass for nonadiposity phenotypes, as covariates. RESULTS: We found strong associations between GAIVS6 and body mass index (p = 0.0001), fat mass (p = 0.0005), percentage body fat (p = 0.0004), the sum of six skinfold thickness (p = 0.0001), and leptin level (p = 0.0001). Homozygote for the GAIVS6 240 bp alleles (15% frequency in QFS) showed higher adiposity than subjects with the GAIVS6 238 bp allele (70% in QFS). The exons, the 5' untranslated region (UTR), and the exon-intron junctions of UCP3 gene from subjects homozygote for either GAIVS6 238 bp or 240 bp alleles were sequenced in search for mutations. Variants 5'UTR-55C-->T and Y210Y(C-->T) were detected, whereas IVS4-36C-->T was uncovered, but no new exonic or splice junction mutation was observed. RFLP Y210Y(C-->T) was not associated to adiposity in QFS; V1021(G-->A) showed no variation. CONCLUSION: Our results suggest that some alleles of UCP3 are involved in the etiology of human obesity.

Randomized, double-blind, placebo-controlled trial of the immune modulator WF10 in patients with advanced AIDS.

A randomized, double-blind trial compared treatment with the immune modulator WF10 (ten patients) and placebo (nine patients) administered in cycles over 3 months among individuals with advanced AIDS. There were no notable clinical adverse events; changes in hematologic and chemistry values were comparable in the two groups. In both groups, median HIV-RNA PCR values remained stable. Immunologic variables showed a consistent tendency to increase in the WF10 group and to decrease in the control group, with significant differences between groups for median WBC, lymphocyte, CD19, and CD35 values. Ten infections occurred in the control group, four of which were Pneumocystis carinii pneumonia (PCP), and three in the WF10 group none of which was PCP. Five patients in the control group were hospitalized during the trial for a total of 53 days; no patients in the WF10 group were hospitalized. Over a subsequent 9-months follow-up, six patients from the control group and one from the WF10 group died. These results indicate that WF10 administration appears safe, may enhance immunologic function, and unlike other macrophage-activating cytokines does not increase HIV expression in this patient population. Further studies of WF10 in larger patient populations are warranted.

Uncoupling protein-3 expression in rodent skeletal muscle is modulated by food intake but not by changes in environmental temperature.

A new member of the uncoupling protein (UCP) family called UCP3 has recently been cloned and shown to be highly expressed in skeletal muscle of rodents and humans. In the present study, UCP3 was overexpressed in C2C12 myoblasts where it acts as an uncoupling protein. Changes in UCP3 mRNA expression were examined in rodent muscles under conditions known to modulate thermogenesis in brown adipose tissue. In skeletal muscle, UCP3 expression did not change in response to 48 h of cold exposure (6 degrees C), whereas it was decreased by 81% or increased 5.6-fold by 1 week of 50% food restriction or fasting, respectively. It was also decreased by 36% in soleus muscle of obese (fa/fa) as compared with lean Zucker rats. The unexpected rise of UCP3 mRNA level induced by fasting did not change in vitro muscle basal heat production rate but decreased by 31% the capacity to produce heat in response to the uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone. This decrease may reflect underlying uncoupling by UCP3. Up-regulation of UCP3 mRNA after a 24-h fast was still observed in mice exposed at thermoneutrality. These results show that the increase in UCP3 expression induced by fasting is associated with the maintenance of thermogenesis measured in muscle in vitro and is not modulated by environmental temperature. The notion that UCP3 expression is modulated by food intake is of importance to better understand the pathophysiology of obesity in humans.

[Biodegradable controlled-release 5-FU implant in the surgery for glaucoma. Experimental study]. / Implant biodégradable à libération contrôlée de 5-FU dans la chirurgie du glaucome. Etude expérimentale.

BACKGROUND: 5-Fluorouracil (5-FU) is useful as an adjunct treatment for glaucoma filtering surgery. However, efficacy depends upon maintaining sustained drug levels, currently achieved by repeated daily injections of the drug for several days. To overcome this limitation, we designed a biodegradable implant for the sustained release of 5-FU. MATERIAL AND METHODS: The implant (0.79 mm diameter, 6 mm long, 2.2 mg weight) contains 0.66 mg of 5-FU and is loaded in a needle coupled to a custom-made instrument to permit subconjonctival insertion of the implant through a 2 mm wide snip incision. The in vitro and in vivo pharmacokinetics as well as the biocompatibility studies of the implants were assessed in the rabbit. RESULTS: No infection, inflammatory reaction or extrusion occurred. The implant released the drug at a constant rate of 1.20 micrograms/hr for over 18 days and totally biodegraded in less than 86 days. CONCLUSION: Implantation of the device, after laser sclerostomy or conventional trabeculectomy shows great potential for the treatment of glaucoma. To determine the implant's efficacy, additional studies in the cat are underway.

[Results of a 2-year animal experiment with reticulated polyethylene oxide intrastromal rings]. / Les résultats de 2 ans d'expérimentation animale des anneaux intrastromaux en polyoxyde d'éthylène réticulé.

Gel Injection Adjustable Keratoplasty (GIAK) is a technique previously described by G. Simon for the correction of myopia. Following pachometry, a 0.8 mm wide, 80% deep linear incision is performed 2.5 mm from the apex. Using a guide, a 1 mm wide, 5 mm diameter annular spatula is introduced to dissect an interlamellar canal and the crosslinked polyethylene oxide hydrogel is injected with a modified 23 gauge needle. The biocompatibility to 13 PEO batches was studied on 21 albino rabbits (Follow up 15 to 135 days). In nineteen, the cornea remained perfectly transparent. Two animals presented an infection at POD 1. Histopathology showed no endothelial deterioration, no anomaly of the thickness or of the cellular morphology around the injected zone. However some mononuclear cells were noticed surrounding the hydrogel in some rabbits together with thinning of the corneal epithelium anterior to the injected zone. A pilot refractive study was conducted on 5 cats using 2 PEO gels. One cat developed an infection following surgery. A second developed an inflammatory response with corneal neovascularization at POD 8. Thus, these animals were not included in the follow-up study which ranged from 6 to 28 months. Immediately after surgery, the refractive effect, measured with the Canon SK-1 digital autokeratometer, was 5.22 +/- 0.46 D (SD) of flattening. The long term effect (26 months) of the GIAK procedure appears to be stable and safe when using sterile PEO gels made of highly purified materials.