American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults.

BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings. CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sß0 (HbSß0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSß0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

Mass Measurement of 56Sc Reveals a Small A = 56 Odd-Even Mass Staggering, Implying a Cooler Accreted Neutron Star Crust.

We present the mass excesses of (52-57)Sc, obtained from recent time-of-flight nuclear mass measurements at the National Superconducting Cyclotron Laboratory at Michigan State University. The masses of 56Sc and 57Sc were determined for the first time with atomic mass excesses of -24.85(59)((-54)(+0)) MeV and -21.0(1.3) MeV, respectively, where the asymmetric uncertainty for 56Sc was included due to possible contamination from a long-lived isomer. The 56Sc mass indicates a small odd-even mass staggering in the A = 56 mass chain towards the neutron drip line, significantly deviating from trends predicted by the global FRDM mass model and favoring trends predicted by the UNEDF0 and UNEDF1 density functional calculations. Together with new shell-model calculations of the electron-capture strength function of 56Sc, our results strongly reduce uncertainties in model calculations of the heating and cooling at the 56Ti electron-capture layer in the outer crust of accreting neutron stars. We find that, in contrast to previous studies, neither strong neutrino cooling nor strong heating occurs in this layer. We conclude that Urca cooling in the outer crusts of accreting neutron stars that exhibit superbursts or high temperature steady-state burning, which are predicted to be rich in A≈56 nuclei, is considerably weaker than predicted. Urca cooling must instead be dominated by electron capture on the small amounts of adjacent odd-A nuclei contained in the superburst and high temperature steady-state burning ashes. This may explain the absence of strong crust Urca cooling inferred from the observed cooling light curve of the transiently accreting x-ray source MAXI J0556-332.

Synergistic induction of apoptosis in high-risk DLBCL by BCL2 inhibition with ABT-199 combined with pharmacologic loss of MCL1.

Better treatments are needed for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of failing standard therapy. Avoiding apoptosis is a hallmark of cancer, and in DLBCL the redundantly functioning antiapoptotic proteins BCL2 and MCL1 are frequently expressed. Here we explore drugs that cause loss of MCL1, particularly the potent new cyclin-dependent kinase inhibitor dinaciclib, which knocks down MCL1 by inhibiting CDK9. Dinaciclib induces apoptosis in DLBCL cells but is completely overcome by increased activity of BCL2. We find that clinical samples have frequent co-expression of MCL1 and BCL2, suggesting that therapeutic strategies targeting only one will lead to treatment failures owing to activity of the other. The BH3 mimetic ABT-199 potently and specifically targets BCL2. Single-agent ABT-199 had modest antitumor activity against most DLBCL lines and resulted in compensatory upregulation of MCL1 expression. ABT-199 synergized strongly, however, when combined with dinaciclib and with other drugs affecting MCL1, including standard DLBCL chemotherapy drugs. We show potent antitumor activities of these combinations in xenografts and in a genetically accurate murine model of MYC-BCL2 double-hit lymphoma. In sum, we reveal a rational treatment paradigm to strip DLBCL of its protection from apoptosis and improve outcomes for high-risk patients.

Mass measurements demonstrate a strong N=28 shell gap in argon.

We present results from recent time-of-flight nuclear mass measurements at the National Superconducting Cyclotron Laboratory at Michigan State University. We report the first mass measurements of ^{48}Ar and ^{49}Ar and find atomic mass excesses of -22.28(31) MeV and -17.8(1.1) MeV, respectively. These masses provide strong evidence for the closed shell nature of neutron number N=28 in argon, which is therefore the lowest even-Z element exhibiting the N=28 closed shell. The resulting trend in binding-energy differences, which probes the strength of the N=28 shell, compares favorably with shell-model calculations in the sd-pf shell using SDPF-U and SDPF-MU Hamiltonians.

No virological evidence for an influenza A - like virus in European bats.

New members of the influenza A virus genus have been detected recently in bats from South America. By molecular investigations, using a generic real-time RT-PCR (RT-qPCR) that detects all previously known influenza A virus subtypes (H1-H16) and a newly developed RT-qPCR specific for the South American bat influenza-like virus of subtype H17, a total of 1571 samples obtained from 1369 individual bats of 26 species from Central Europe were examined. No evidence for the occurrence of such influenza viruses was found. Further attempts towards a more comprehensive evaluation of the role of bats in the ecology and epidemiology of influenza viruses should be based on more intense monitoring efforts. However, given the protected status of bats, not only in Europe, such activities need to be embedded into existing pathogen-monitoring programs.

Lyssavirus distribution in naturally infected bats from Germany.

In Germany, to date three different lyssavirus species are responsible for bat rabies in indigenous bats: the European Bat Lyssaviruses type 1 and 2 (EBLV-1, EBLV-2) and the Bokeloh Bat Lyssavirus (BBLV) for which Eptesicus serotinus, Myotis daubentonii and Myotis nattereri, respectively, are primary hosts. Lyssavirus maintenance, evolution, and epidemiology are still insufficiently explored. Moreover, the small number of bats infected, the nocturnal habits of bats and the limited experimental data still hamper attempts to understand the distribution, prevalence, and in particular transmission of the virus. In an experimental study in E. serotinus a heterogeneous dissemination of EBLV-1 in tissues was detected. However, it is not clear whether the EBLV-1 distribution is similar in naturally infected animals. In an attempt to further analyze virus dissemination and viral loads within naturally infected hosts we investigated tissues of 57 EBLV-1 positive individuals of E. serotinus from Germany by RT-qPCR and compared the results with those obtained experimentally. Additionally, tissue samples were investigated with immunohistochemistry to detect lyssavirus antigen in defined structures. While in individual animals virus RNA was present only in the brain, in the majority of E. serotinus viral RNA was found in various tissues with highest relative viral loads detected in the brain. Interestingly, viral antigen was confirmed in various tissues in the tongue including deep intralingual glands, nerves, muscle cells and lingual papillae. So, the tongue appears to be a prominent site for virus replication and possibly shedding.

Twenty years of active bat rabies surveillance in Germany: a detailed analysis and future perspectives.

SUMMARY: In Germany, active bat rabies surveillance was conducted between 1993 and 2012. A total of 4546 oropharyngeal swab samples from 18 bat species were screened for the presence of EBLV-1- , EBLV-2- and BBLV-specific RNA. Overall, 0·15% of oropharyngeal swab samples tested EBLV-1 positive, with the majority originating from Eptesicus serotinus. Interestingly, out of seven RT-PCR-positive oropharyngeal swabs subjected to virus isolation, viable virus was isolated from a single serotine bat (E. serotinus). Additionally, about 1226 blood samples were tested serologically, and varying virus neutralizing antibody titres were found in at least eight different bat species. The detection of viral RNA and seroconversion in repeatedly sampled serotine bats indicates long-term circulation of the virus in a particular bat colony. The limitations of random-based active bat rabies surveillance over passive bat rabies surveillance and its possible application of targeted approaches for future research activities on bat lyssavirus dynamics and maintenance are discussed.

Bat rabies surveillance in Europe.

Rabies is the oldest known zoonotic disease and was also the first recognized bat associated infection in humans. To date, four different lyssavirus species are the causative agents of rabies in European bats: the European Bat Lyssaviruses type 1 and 2 (EBLV-1, EBLV-2), the recently discovered putative new lyssavirus species Bokeloh Bat Lyssavirus (BBLV) and the West Caucasian Bat Virus (WCBV). Unlike in the new world, bat rabies cases in Europe are comparatively less frequent, possibly as a result of varying intensity of surveillance. Thus, the objective was to provide an assessment of the bat rabies surveillance data in Europe, taking both reported data to the WHO Rabies Bulletin Europe and published results into account. In Europe, 959 bat rabies cases were reported to the RBE in the time period 1977-2010 with the vast majority characterized as EBLV-1, frequently isolated in the Netherlands, North Germany, Denmark, Poland and also in parts of France and Spain. Most EBLV-2 isolates originated from the United Kingdom (UK) and the Netherlands, and EBLV-2 was also detected in Germany, Finland and Switzerland. Thus far, only one isolate of BBLV was found in Germany. Published passive bat rabies surveillance comprised testing of 28 of the 52 different European bat species for rabies. EBLV-1 was isolated exclusively from Serotine bats (Eptesicus serotinus and Eptesicus isabellinus), while EBLV-2 was detected in 14 Daubenton's bats (Myotis daubentonii) and 5 Pond bats (Myotis dasycneme). A virus from a single Natterer's bat (Myotis nattereri) was characterized as BBLV. During active surveillance, only oral swabs from 2 Daubenton's bats (EBLV-2) and from several Eptesicus bats (EBLV-1) yielded virus positive RNA. Virus neutralizing antibodies against lyssaviruses were detected in various European bat species from different countries, and its value and implications are discussed.

[Dental care and sexuality]. / Médecine dentaire esthétique et sexualité.

It must be stressed that a comprehensive evaluation of the general health condition is a pre-requisite in any screening process of a specific sexual activity. In the same way, the oral health examination should include the soft tissues such as the tongue and the lips, and the oral breath as well as the teeth to stress their possible implication in disorders of any kind. A special attention is given to the connexion between a good sexual life and a good aspect of all the dentition. The main purpose is to presume the importance particularly of smile, kisses and a good breath in the sexual life of a couple.

Case report: periosteal osteosarcoma of the clavicle.

Periosteal osteosarcomas are rare and usually affect the meta-diaphyseal region of long bones. We present a case of a periosteal osteosarcoma of the clavicle, a highly unusual site and representing one of only two such cases documented in the English literature. This case illustrates the diagnostic dilemmas in the classification of such tumors, particularly in small biopsy specimens from unusual locations. It emphasizes the importance of radiological and pathological correlation.

[Acute subglottic tracheal stenosis after resuscitation]. / Akute subglottische Trachealstenose nach Reanimation.

Following cardiac arrest a 41-year-old patient was resuscitated for 40 min and required mechanical ventilation for 27.5 h. Acute shortness of breath and inspiratory stridor developed 7 days after successful extubation. Bronchoscopy revealed a subtotal tracheal stenosis caused by extensive fibrinous membranes. Local ischaemia caused by cuff pressure seems to be a likely explanation with an additional component of general hypoperfusion and haemodynamic instability which led to gastric bleeding (classification according to Forrest IIc) from ischaemic ulcers.

[Surgical treatment of pulmonary aspergilloma]. / Die chirurgische Therapie des pulmonalen Aspergilloms.

Invasive pulmonary aspergillosis is a life-threatening disease, developing from infection mostly by Aspergillus fumigatus. It is an opportunistic infection and occurs mostly in immunosuppressed patients, after tuberculosis, in patients with AIDS or malignomas. The most common symptom and complication is hemoptysis up to massive bleeding. Surgical treatment is obligatory on patients with a pulmonary aspergilloma. Time and form of intervention should be discussed between surgeon and pulmonologist. Resection should follow anatomical borders like lobectomy or pneumectomy. Any remaining intrathoracic cavities should be filled either with remaining lung tissue or with muscle flaps of latissimus or pectoralis muscle or omentum majus. Following these rules, intervention can be performed with reasonable mortality and morbidity rate.

Long-term vertical changes of the anterior maxillary teeth adjacent to single implants in young and mature adults. A retrospective study.

AIM: To evaluate the effects of the tooth eruption process on the position of teeth adjacent to implant-borne restorations in adult patients compared to patients in their late adolescence. SUBJECT AND METHODS: The sample included 28 patients divided into two groups. A "young adult" group consisting of 14 patients, aged from 15.5 to 21 years, and a "mature adult" group consisting of 14 patients, aged from 40 to 55 years. All patients presented missing anterior teeth, requiring insertion of 40 implant fixtures (16 central incisors, 12 lateral incisors, 12 canines). The implants were of the Straumann Dental Implant System, clinically and radiologically re-evaluated 1 year or more after the surgical procedure (mean interval=4.2 years). Assessment of the eruption of the adjacent teeth was performed using the implant as a stable point of reference: measurements of the different reference points were compared after implant placement and at follow-up examination. RESULTS: In the "young adult" group, all patients showed infra-occlusion of the implant-supported crowns: the vertical step measured on radiographs varied between 0.1 and 1.65 mm. In the "mature adult" group, all patients showed a vertical difference between the teeth adjacent to the implant-supported crown and the implant: the measured step ranged from 0.12 to 1.86 mm. No difference was found in the amount of vertical eruption between male and female patients, nor according to localization of the implant. CONCLUSION: Mature adults can exhibit major vertical steps after anterior restorations with osseointegrated fixtures to the same extent as adolescents or "young adult" individuals with residuous growth potential.

[Plastic bronchitis]. / Bronchitis plastica.

Bronchitis plastica is a rare disorder that can occur at any age. It is characterised by formation of large, branching bronchial casts, which are often expectorated, but may be discovered only by bronchoscopy. In most cases, bronchial casts are secondary to underlying diseases of the lung, heart or lymph vessels. We report a case of plastic bronchitis associated with bilateral chylothorax. Progressive respiratory failure could be controlled by repeated bronchoscopic extraction of casts and inhalation of 20,000 units of heparin twice a day. Inhalation of heparin should be considered, when treatment of the underlying disorders is not successful and the casts consist largely of fibrin. Histological examination of the casts may be useful for therapeutic decisions and can point additionally to an underlying disease.

Epiphyseal osteoblastoma-like osteosarcoma.

Osteoblastoma-like osteosarcoma is a rare variant of osteosarcoma occurring in this instance in a highly unusual location: the lateral femoral condyle of a 13-year-old girl. The radiological features were non-aggressive and, although slightly unusual, were most suggestive of chondroblastoma.

Inhibition of return in children with perinatal brain injury.

Inhibition of return is a bias in attention that reduces the likelihood of returning attention to previously viewed locations. This attention bias develops during the first 6 months of life and is putatively mediated by midbrain structures. The present study evaluated the effects of perinatal lesions on the development of inhibition of return. Thirty-three children with perinatal injury resulting in spastic diplegic cerebral palsy were grouped based on magnetic resonance exams. Children with anterior (n = 5), posterior (n = 12), diffuse (n = 8), or no apparent (n = 8) lesions were compared with a group of age-matched children without neurologic injury (n = 39) on an orienting task designed to elicit inhibition of return. Short-delay trials demonstrated grossly intact facilitation of attention for all groups. Long-delay trials that produced inhibition of return in the control and posterior injury groups indicated a disruption of inhibition of return in the groups with anterior and diffuse lesions. The findings are consistent with previous reports that anterior regions are important for the developing attention system, and that bilateral injury can result in unilateral disruption of visual attention.

Poor school and cognitive functioning with silent cerebral infarcts and sickle cell disease.

The authors evaluated education attainment and neuropsychological deficits in children with sickle cell disease (SCD) and silent cerebral infarcts. Children with silent infarcts had twice the rate of school difficulties as children without infarcts. Eighty percent of silent infarct cases had clinically significant cognitive deficits, whereas 35% had deficits in academic skills. Children with silent cerebral infarcts show high rates of poor educational attainment, cognitive deficits, and frontal lobe injury. Poor school performance in SCD is one indicator of silent infarcts.

Intramolecular [4 + 2] cycloaddition reaction of six- and seven-membered cyclic N-allyl-C-arylethynyl iminium salts.

N-Allyl-2-(het)arylethynyl-3,4,5,6-tetrahydropyridinium triflates 1c,d,e and N-allyl-2-(het)aryl-4,5,6,7-tetrahydro-3H-azepinium triflates 1g,h undergo a thermal isomerization reaction leading to derivatives of [a,f]-annulated isoindolium salts 2 in good yields. Similarly, N-allyl-2-phenylethynyl-pyridinium triflate 4 is transformed into the condensed pyridinium salt 5. An intramolecular [4 + 2] cycloaddition reaction, in which the (het)arylethynyl moiety acts as the 4pi component, is considered as the key step of this transformation. In contrast, the related N-allyl-4,5-dihydro-3H-pyrrolium salts 1a,b and N-homoallyl-3,4,5,6-tetrahydropyridinium salt 1f undergo unspecific decomposition under thermal impact.

[Role of surgical procedures in the diagnosis and therapy of tuberculosis]. / Stellenwert chirurgischer Operationsverfahren bei der Diagnostik und Therapie der Tuberkulose.

Over the last decades the annual number of surgical intervention for treatment of pulmonary tuberculosis has steadily declined. Despite effective antituberculotic medication, there are still indications for thoracic surgery. The aim of the present study was to give an account of the diagnostic and therapeutic role of surgery of pulmonary tuberculosis. Therefore we analysed all operated patients with pulmonary tuberculosis between 1988 and 1999. In 2% of all patients with pulmonary tuberculosis surgical intervention was performed (n = 35). Their main indication was resection for suspected carcinoma, multi-drug resistance or non-compliance to the medical treatment, decortication because of cavern rupture or empyema, hemoptoe and destroyed lung. A additional indication for surgery was pulmonary aspergilloma caused by superinfection of postspecific cavities. Postoperative complications like bleeding (> 1000 ml) or broncho-pleural fistula occurred in 37%, none of the patients died. Surgery is still a valid option für the treatment of pulmonary tuberculosis. Before surgical intervention, a long term antituberculotic chemotherapy is essential. Patients have to be selected individually because of an increased morbidity. In 10% of all operated patients (n = 1132) with preoperative unidentifiable pulmonary mass the infiltrate was specific aetiology.