A comparison of simplified protocols of personalized dosimetry in NEN patients treated by radioligand therapy (RLT) with [177Lu]Lu-DOTATATE to favor its use in clinical practice.

The role of internal dosimetry is usually proposed for investigational purposes in patients treated by RLT, even if its application is not yet the standard method in clinical practice. This limited use is partially justified by several concomitant factors that make calculations a complex process. Therefore, simplified dosimetry protocols are required. METHODS: In our study, dosimetric evaluations were performed in thirty patients with NENs who underwent RLT with [177Lu]Lu-DOTATATE. The reference method (M0) calculated the cumulative absorbed dose performing dosimetry after each of the four cycles. Obtained data were employed to assess the feasibility of simplified protocols: defining the dosimetry only after the first cycle (M1) and after the first and last one (M2). RESULTS: The mean differences of the cumulative absorbed doses between M1 and M0 were - 10% for kidney, - 5% for spleen, + 34% for liver, + 13% for red marrow, and + 37% for tumor lesions. Conversely, differences lower than ± 10% were measured between M2 and M0. CONCLUSION: Cumulative absorbed doses obtained with the M2 protocol resembled the doses calculated by M0, while the M1 protocol overestimated the absorbed doses in all organs at risk, except for the spleen.

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer.

The aim of this work is to compare [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 PET/CT as imaging agents in patients with prostate cancer (PCa). Comparisons were made by evaluating times and costs of the radiolabeling process, imaging features including pharmacokinetics, and impact on patient management. The analysis of advantages and drawbacks of both radioligands might help to make a better choice based on firm data. For [68Ga]Ga-PSMA-11, the radiochemical yield (RCY) using a low starting activity (L, average activity of 596.55 ± 37.97 MBq) was of 80.98 ± 0.05%, while using a high one (H, average activity of 1436.27 ± 68.68 MBq), the RCY was 71.48 ± 0.04%. Thus, increased starting activities of [68Ga]-chloride negatively influenced the RCY. A similar scenario occurred for [18F]PSMA-1007. The rate of detection of PCa lesions by Positron Emission Tomography/Computed Tomography (PET/CT) was similar for both radioligands, while their distribution in normal organs significantly differed. Furthermore, similar patterns of biodistribution were found among [18F]PSMA-1007, [68Ga]Ga-PSMA-11, and [177Lu]Lu-PSMA-617, the most used agent for RLT. Moreover, the analysis of economical aspects for each single batch of production corrected for the number of allowed PET/CT examinations suggested major advantages of [18F]PSMA-1007 compared with [68Ga]Ga-PSMA-11. Data from this study should support the proper choice in the selection of the PSMA PET radioligand to use on the basis of the cases to study.

Cognitive Improvement After Cochlear Implantation in Older Adults With Severe or Profound Hearing Impairment: A Prospective, Longitudinal, Controlled, Multicenter Study.

OBJECTIVE: To compare the cognitive evolution of older adults with severe or profound hearing impairment after cochlear implantation with that of a matched group of older adults with severe hearing impairment who do not receive a cochlear implant (CI). DESIGN: In this prospective, longitudinal, controlled, and multicenter study, 24 older CI users were included in the intervention group and 24 adults without a CI in the control group. The control group matched the intervention group in terms of gender, age, formal education, cognitive functioning, and residual hearing. Assessments were made at baseline and 14 months later. Primary outcome measurements included the change in the total score on the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing impaired individuals score and on its subdomain score to assess cognitive evolution in both groups. Secondary outcome measurements included self-reported changes in sound quality (Hearing Implant Sound Quality Index), self-perceived hearing disability (Speech, Spatial, and Qualities of Hearing Scale), states of anxiety and depression (Hospital Anxiety and Depression Scale), and level of negative affectivity and social inhibition (Type D questionnaire). RESULTS: Improvements of the overall cognitive functioning (p = 0.05) and the subdomain "Attention" (p = 0.02) were observed after cochlear implantation in the intervention group; their scores were compared to the corresponding scores in the control group. Significant positive effects of cochlear implantation on sound quality and self-perceived hearing outcomes were found in the intervention group. Notably, 20% fewer traits of Type D personalities were measured in the intervention group after cochlear implantation. In the control group, traits of Type D personalities increased by 13%. CONCLUSION: Intervention with a CI improved cognitive functioning (domain Attention in particular) in older adults with severe hearing impairment compared to that of the matched controls with hearing impairment without a CI. However, older CI users did not, in terms of cognition, bridge the performance gap with adults with normal hearing after 1 year of CI use. The fact that experienced, older CI users still present subnormal cognitive functioning may highlight the need for additional cognitive rehabilitation in the long term after implantation.

Evaluation of the auricular surface method for subadult sex estimation on Italian modern (19th to 20th century) identified skeletal collections.

OBJECTIVES: Sex estimation in subadult skeletal remains is still considered highly problematic. The aim of this research is to test the reliability of the method of subadult sex assessment proposed by Luna and co-workers in 2017, based on the analysis of the auricular surface of the ilium. MATERIALS AND METHODS: Seven ratios and three morphological traits were recorded for 127 subadult individuals (63 males and 64 females), aged between 0 and 17 years, from several Identified Skeletal Collections of the University of Bologna. Nonparametric Mann Whitney test, Kolmogorov Smirnov test, and the Pearson correlation coefficient were used for continuous variables, whereas the Cramer Coefficient was calculated for qualitative variable. A principal component analysis was also performed on ratio values. The statistic ƞ was taken into account for both types of variables. RESULTS: None of the ratios presented significant dimorphic results. Two qualitative variables show statistically significant differences between sexes. The overall morphology proved to be an accurate sex predictor among children aged ≥4 years (78%-86%) and meets the minimum accuracy standard (75%) for subadult sex estimation for individuals between 1 and 17 years of age. The morphology of the retroauricular end of the superior demiface (MRS) can be used with a high level of accuracy for sexing individuals from 1 to 12 years (77%-81%). CONCLUSIONS: The metric variables did not replicate the accuracy values originally obtained by Luna and co-workers. Otherwise, the evaluation of the morphological variables proposed by the authors yielded promising results as a reliable sexing technique for individuals who died before puberty.

Small-bowel capsule endoscopy with panoramic view: results of the first multicenter, observational study (with videos).

BACKGROUND AND AIMS: The first small-bowel video-capsule endoscopy (VCE) with 360° panoramic view has been developed recently. This new capsule has wire-free technology, 4 high-frame-rate cameras, and a long-lasting battery life. The aim of the present study was to assess the performance and safety profile of the 360° panoramic-view capsule in a large series of patients from a multicenter clinical practice setting. METHODS: Consecutive patients undergoing a 360° panoramic-view capsule procedure in 7 European Institutions between January 2011 and November 2015 were included. Both technical (ie, technical failures, completion rate) and clinical (ie, indication, findings, retention rate) data were collected by means of a structured questionnaire. VCE findings were classified according to the likelihood of explaining the reason for referral: P0, low; P1, intermediate; P2, high. RESULTS: Of the 172 patients (94 men; median age, 68 years; interquartile range, 53-75), 142 underwent VCE for obscure (32 overt, 110 occult) GI bleeding (OGIB), and 28 for suspected (17) or established (2) Crohn's disease (CD). Overall, 560 findings were detected; 252 were classified as P2. The overall diagnostic yield was 40.1%; 42.2% and 30.0% in patients with OGIB and CD, respectively. The rate of complete enteroscopy was 90.2%. All patients but one, who experienced capsule retention (1/172, 0.6%), excreted and retrieved the capsule. VCE failure occurred in 4 of 172 (2.3%) patients because of technical problems. CONCLUSIONS: This multicenter study, conducted in the clinical practice setting and based on a large consecutive series of patients, showed that the diagnostic yield and safety profile of the 360° panoramic-view capsule are similar to those of forward-view VCEs.

Transplanted bone marrow mononuclear cells and MSCs impart clinical benefit to children with osteogenesis imperfecta through different mechanisms.

Transplantation of whole bone marrow (BMT) as well as ex vivo-expanded mesenchymal stromal cells (MSCs) leads to striking clinical benefits in children with osteogenesis imperfecta (OI); however, the underlying mechanism of these cell therapies has not been elucidated. Here, we show that non-(plastic)-adherent bone marrow cells (NABMCs) are more potent osteoprogenitors than MSCs in mice. Translating these findings to the clinic, a T cell-depleted marrow mononuclear cell boost (> 99.99% NABMC) given to children with OI who had previously undergone BMT resulted in marked growth acceleration in a subset of patients, unambiguously indicating the therapeutic potential of bone marrow cells for these patients. Then, in a murine model of OI, we demonstrated that as the donor NABMCs differentiate to osteoblasts, they contribute normal collagen to the bone matrix. In contrast, MSCs do not substantially engraft in bone, but secrete a soluble mediator that indirectly stimulates growth, data which provide the underlying mechanism of our prior clinical trial of MSC therapy for children with OI. Collectively, our data indicate that both NABMCs and MSCs constitute effective cell therapy for OI, but exert their clinical impact by different, complementary mechanisms. The study is registered at www.clinicaltrials.gov as NCT00187018.

Transplanted murine long-term repopulating hematopoietic cells can differentiate to osteoblasts in the marrow stem cell niche.

Bone marrow transplantation (BMT) can give rise to donor-derived osteopoiesis in mice and humans; however, the source of this activity, whether a primitive osteoprogenitor or a transplantable marrow cell with dual hematopoietic and osteogenic potential, has eluded detection. To address this issue, we fractionated whole BM from mice according to cell surface immunophenotype and assayed the hematopoietic and osteopoietic potentials of the transplanted cells. Here, we show that a donor marrow cell capable of robust osteopoiesis possesses a surface phenotype of c-Kit(+) Lin(-) Sca-1(+) CD34(-/lo), identical to that of the long-term repopulating hematopoietic stem cell (LTR-HSC). Secondary BMT studies demonstrated that a single marrow cell able to contribute to hematopoietic reconstitution in primary recipients also drives robust osteopoiesis and LT hematopoiesis in secondary recipients. These findings indicate that LTR-HSC can give rise to progeny that differentiate to osteoblasts after BMT, suggesting a mechanism for prompt restoration of the osteoblastic HSC niche following BM injury, such as that induced by clinical BMT preparative regimens. An understanding of the mechanisms that regulate this differentiation potential may lead to novel treatments for disorders of bone as well as methods for preserving the integrity of endosteal hematopoietic niches.

Delayed marrow infusion in mice enhances hematopoietic and osteopoietic engraftment by facilitating transient expansion of the osteoblastic niche.

Transplantation of bone marrow cells leads to engraftment of osteopoietic and hematopoietic progenitors. We sought to determine whether the recently described transient expansion of the host osteoblastic niche after marrow radioablation promotes engraftment of both osteopoietic and hematopoietic progenitor cells. Mice infused with marrow cells 24 hours after total body irradiation (TBI) demonstrated significantly greater osteopoietic and hematopoietic progenitor chimerism than did mice infused at 30 minutes or 6 hours. Irradiated mice with a lead shield over 1 hind limb showed greater hematopoietic chimerism in the irradiated limb than in the shielded limb at both the 6- and 24-hour intervals. By contrast, the osteopoietic chimerism was essentially equal in the 2 limbs at each of these intervals, although it significantly increased when cells were infused 24 hours compared with 6 hours after TBI. Similarly, the number of donor phenotypic long-term hematopoietic stem cells was equivalent in the irradiated and shielded limbs after each irradiation-to-infusion interval but was significantly increased at the 24-hour interval. Our findings indicate that a 24-hour delay in marrow cell infusion after TBI facilitates expansion of the endosteal osteoblastic niche, leading to enhanced osteopoietic and hematopoietic engraftment.

A comparative study of hearing aids and round window application of the vibrant sound bridge (VSB) for patients with mixed or conductive hearing loss.

OBJECTIVE: This study was undertaken to determine the efficacy of the round window (RW) application of the vibrant soundbridge (VSB) in patients with mixed or conductive hearing loss. DESIGN: Speech in quiet and in noise were compared to preoperative data attained with conventional hearing aids so that each subject served as his or her own control in a single test protocol. STUDY SAMPLE: Eighteen adults implanted monaurally with the VSB in the poorer hearing ear. Experience with the VSB ranged from nine to 25 months. RESULTS: Sixteen of the 18 subjects were successful VSB users, wearing their device all waking hours. There was no significant deterioration in the averaged bone conduction results preoperatively versus post-operatively (p>0.05). Speech recognition in quiet results were not significantly different to performance attained whilst wearing hearing aids (p>0.05). Speech recognition in noise performance was substantially improved with use of the VSB in most test conditions. CONCLUSIONS: For the majority of the subjects, the VSB was an effective method of hearing restoration for their mixed and conductive hearing loss.

Results of a Novel, Nonsurgical Bone-Conduction Hearing Aid for the Treatment of Conductive Hearing Loss in Australian Children.

OBJECTIVE: To determine and compare the benefits a novel adhesive bone-conduction system and a conventional bone-conduction hearing aid (BCHA) on a softband for children with conductive hearing loss. STUDY DESIGN: Prospective, single-subject randomized, crossover trial. SETTING: Tertiary referral center in Australia. PARTICIPANTS: Eight children aged from 4 to 17 years with conductive hearing loss. INTERVENTION: Rehabilitative with participants using the novel adhesive bone-conduction aid and a BCHA. MAIN OUTCOME MEASURES: Aided thresholds, as well as speech perception in quiet, unaided and aided with the novel adhesive bone-conduction aid and BCHA on a softband. For the six older children, speech in noise testing was also conducted. RESULTS: The mean unaided four frequency average hearing levels was 48 dB HL for air conduction, 10.5 dB HL for bone conduction, with a mean air-bone gap in the aided ear of 37.5 dB HL.Four-frequency average hearing level aided thresholds were 20.2 dB for the novel device and 19.8 dB for the BCHA, with no significant difference between the devices. Aided monosyllabic word scores improved from an average of 45% in the unaided condition to 81.6 and 85% for the novel adhesive and BCHA devices, respectively. Aided speech in noise performance improved, on average, by 1.6 dB SNR when wearing the BCHA and the novel adhesive device, with no significant difference in performance between the two devices. CONCLUSIONS: The novel device provided equivalent performance to the BCHA on all measures and can be considered as an alternative device for pediatric patients with conductive hearing loss.

Decision making in bone conduction and active middle ear implants - hearing outcomes and experiences over a 10-year period.

OBJECTIVES: To review the decision-making paradigm in the recommendations of BCI and aMEI overlapping candidacy for patients with conductive or mixed HL, and to determine if there are differences in hearing and quality of life outcomes between these implantable hearing devices. METHODS: Retrospective data from patients receiving BCI or aMEI in the past decade were analysed. Patients were grouped into: 1. BCI candidates, 2. BCI or aMEI candidates, and 3. aMEI candidates. We compared outcomes and examined the impact of BC threshold, age at implantation, and duration of hearing loss on candidacy. RESULTS: 89 participants were included: 30 BCI, 37 aMEI, and 22 BCI or aMEI candidates. All groups performed similarly in aided sound field threshold testing. BCI group had lower speech scores in quiet compared to 'BCI or aMEI.' No significant differences were found in APHAB global scores. BC threshold, duration of hearing loss, and age at implantation had no significant effects. DISCUSSION: Outcomes were generally similar across groups, except for higher effective gain in the aMEI group. CONCLUSION: Our proposed patient pathway and decision-making approach facilitate candidate selection for aMEI and BCI, aiming to optimise outcomes.

Delayed resolution of lung inflammation in Il-1rn-/- mice reflects elevated IL-17A/granulocyte colony-stimulating factor expression.

IL-1 has been associated with acute lung injury (ALI) in both humans and animal models, but further investigation of the precise mechanisms involved is needed, and may identify novel therapeutic targets. To discover the IL-1 mediators essential to the initiation and resolution phases of acute lung inflammation, knockout mice (with targeted deletions for either the IL-1 receptor-1, i.e., Il-1r1(-/-), or the IL-1 receptor antagonist, i.e., Il-1rn(-/-)) were exposed to aerosolized LPS, and indices of lung and systemic inflammation were examined over the subsequent 48 hours. The resultant cell counts, histology, protein, and RNA expression of key cytokines were measured. Il-1r1(-/-) mice exhibited decreased neutrophil influx, particularly at 4 and 48 hours after exposure to LPS, as well as reduced bronchoalveolar lavage (BAL) expression of chemokines and granulocyte colony-stimulating factor (G-CSF). On the contrary, Il-1rn(-/-) mice demonstrated increased BAL neutrophil counts, increased BAL total protein, and greater evidence of histologic injury, all most notably 2 days after LPS exposure. Il-1rn(-/-) mice also exhibited higher peripheral neutrophil counts and greater numbers of granulocyte receptor-1 cells in their bone marrow, potentially reflecting their elevated plasma G-CSF concentrations. Furthermore, IL-17A expression was increased in the BAL and lungs of Il-1rn(-/-) mice after exposure to LPS, likely because of increased numbers of γδ T cells in the Il-1rn(-/-) lungs. Blockade with IL-17A monoclonal antibody before LPS exposure decreased the resultant BAL neutrophil counts and lung G-CSF expression in Il-1rn(-/-) mice, 48 hours after exposure to LPS. In conclusion, Il-1rn(-/-) mice exhibit delayed resolution in acute lung inflammation after exposure to LPS, a process that appears to be mediated via the G-CSF/IL-17A axis.

Tinnitus and quality of life after round window vibroplasty.

OBJECTIVE: To measure the Quality of Life outcomes and impact on tinnitus perception in a group of patients after Round Window Vibroplasty (RW-VSB) for mixed or conductive hearing loss. STUDY DESIGN: A single-subject, repeated measures design was employed. All VSB fittings were based on hearing thresholds results and were not set to mask tinnitus. METHODS: Ten Round Window-Vibroplasty patients were assessed with the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Tinnitus Reaction Questionnaire (TRQ). RESULTS: Subjects reported less hearing difficulties in 3 of 4 APHAB subscales. Tinnitus perception was decreased in all subjects with tinnitus pre-operatively. CONCLUSION: Round window vibroplasty in our cohort of patients with mixed or conductive hearing improved quality of life outcomes. There was significant improvement on APHAB scores and a significant decrease in tinnitus perception in subjects experiencing tinnitus prior to implantation.

Cortical auditory evoked potential in cochlear implant users: An objective method to improve speech perception.

OBJECTIVE: To investigate if cortical auditory evoked potential (CAEP) measures can be used to verify the cochlear implant (CI) map and consequently improve CI outcomes in adults with bilateral hearing loss. DESIGN: CAEPs were measured in CI recipients using the speech tokens /m/, /g/, /t/ and /s/. If CAEP responses were present for all speech tokens, the participant's map was considered "satisfactory". If CAEP responses were absent, the CI map was considered "unsatisfactory" and therefore adjusted and CAEP measures repeated. This was repeated until auditory potentials were seen in response to all four speech tokens. Speech testing was conducted pre-CI, as well as before and after CAEP-guided map adjustments. RESULTS: 108 adult unilateral CI users participated, whose sound processors were previously programmed using subjective methods. 42 CI users elicited a CAEP response to all four speech tokens and therefore no further mapping adjustments were made. 66 subjected lacked a CAEP response to at least one speech token and had their CI map adjusted accordingly. Of those, 31 showed a CAEP response to all four speech tokens, and the average speech score significantly improved after CI map adjustments based on CAEP responses. CONCLUSION: CAEP's are an objective tool that can be used to guide and verify CI mapping in adults CI users. Significant improvement in speech scores was observed in participants who had their CI map adjusted based on CAEP responses.

SIMEU position paper on non-invasive respiratory support in COVID-19 pneumonia.

The rapid worldwide spread of the Coronavirus disease (COVID-19) crisis has put health systems under pressure to a level never experienced before, putting intensive care units in a position to fail to meet an exponentially growing demand. The main clinical feature of the disease is a progressive arterial hypoxemia which rapidly leads to ARDS which makes the use of intensive care and mechanical ventilation almost inevitable. The difficulty of health systems to guarantee a corresponding supply of resources in intensive care, together with the uncertain results reported in the literature with respect to patients who undergo early conventional ventilation, make the search for alternative methods of oxygenation and ventilation and potentially preventive of the need for tracheal intubation, such as non-invasive respiratory support techniques particularly valuable. In this context, the Emergency Department, located between the area outside the hospital and hospital ward and ICU, assumes the role of a crucial junction, due to the possibility of applying these techniques at a sufficiently early stage and being able to rapidly evaluate their effectiveness. This position paper describes the indications for the use of non-invasive respiratory support techniques in respiratory failure secondary to COVID-19-related pneumonia, formulated by the Non-invasive Ventilation Faculty of the Italian Society of Emergency Medicine (SIMEU) on the base of what is available in the literature and on the authors' direct experience. Rationale, literature, tips & tricks, resources, risks and expected results, and patient interaction will be discussed for each one of the escalating non-invasive respiratory techniques: standard oxygen, HFNCO, CPAP, NIPPV, and awake self-repositioning. The final chapter describes our suggested approach to the failing patient.

On site production of [18F]PSMA-1007 using different [18F]fluoride activities: practical, technical and economical impact.

BACKGROUND: Prostate-specific membrane antigen is overexpressed in prostate cancer and it is considered a good target for positron emission tomography/computed tomography imaging of primary cancer and recurrent/metastatic disease, as well as for radioligand therapy. Different PSMA-analogues labeled with [68Ga]gallium have been investigated, showing excellent imaging properties; however, only small amounts can be produced for each radiolabeling. Recently, a [18F]fluoride labeled PSMA-inhibitor, [18F]PSMA-1007, has been introduced, and it has ensured large-scale productions, overcoming this limitation of [68Ga]PSMAs. In this study, PSMA-1007 has been labeled with low (A), medium (B) and high (C) starting activities of [18F]fluoride, in order to verify if radiochemical yield, radiochemical purity and stability of [18F]PSMA-1007 were affected. These parameters have been measured in sixty-five consecutive batches. In addition, the estimation of [18F]PSMA-1007 production costs is provided. RESULTS: The radiochemical yield for low and medium activities of [18F]fluoride was 52%, while for the high one it decreased to 40%. The radiochemical purity was 99% for all three activities. [18F]PSMA-1007 did not show radiolysis up to 8 h after the end of synthesis, confirming that the radiopharmaceutical is stable and suitable to perform diagnostic studies in humans for a long period of time after the end of radiolabeling. Furthermore, radiochemical stability was demonstrated in fetal bovine serum at 4 °C and 37 °C for 120'. CONCLUSIONS: A starting activity of [18F]fluoride of 90 GBq (B) seems to be the best option enabling a final amount of about of 50 GBq of [18F]PSMA-1007, which is promising as it allows to: (a) perform a large number of scans, and/or (b) supply the radiopharmaceutical to any peripheral diagnostic centers in need.

The Use of a Novel, Nonsurgical Bone Conduction Hearing Aid System for the Treatment of Conductive Hearing Loss.

OBJECTIVE: Conventional bone conduction hearing aid solutions often require a cumbersome retention system such as a headband or cap. This study aims to determine if a novel, nonsurgical bone conduction aid utilizing an adhesive attachment over the mastoid is equivalent to the conventional bone conduction hearing aid (BCHA) for the management of conductive hearing loss. STUDY DESIGN: Prospective, single-subject randomized, crossover trial. SETTING: Tertiary referral center. PATIENTS: Eleven adults and 1 child between 11 and 70 years of age with unilateral conductive hearing loss were enrolled. INTERVENTION: Patients had their baseline hearing assessed and were randomized to receive either the novel device or BCHA headband system. Hearing loss etiologies were varied and included cholesteatoma, otosclerosis, chronic otitis media, and previous head and neck surgery. Patients had their baseline hearing assessed and trialled both the novel device or the BCHA headband system. Patients were randomly assigned one device which was worn for 2 weeks followed by a 2-week trial with the alternate device. MAIN OUTCOME MEASURE: Pure-tone thresholds and speech discrimination in quiet and noise were tested and patients also completed the short form of the Speech Spatial and Quality of Hearing (SSQ) questionnaire. RESULTS: The mean unaided 4 frequency pure-tone average (PTA) air conduction threshold was 53.9 dB, bone conduction was 11.9 dB, and the mean air bone gap was 42 dB in the target ear. One patient with an adhesive skin reaction could not complete the protocol. Aided PTA and threshold testing between 250 Hz to 8000 Hz showed statistically equivalent results between both devices. The aided CNC word score, signal-to-noise ratio, and SSQ scores were also equivalent between both devices. CONCLUSION: The novel bone conduction aid demonstrates equivalent performance to the conventional BCHA headband solution. The novel device should be considered an alternative option where the cosmetic and comfort issues of a headband worn device are a concern.

Transplantable marrow osteoprogenitors engraft in discrete saturable sites in the marrow microenvironment.

OBJECTIVE: Based on the recognition that marrow contains progenitors for bone as well as blood, we undertook the first trial of bone marrow transplantation (BMT) for a genetic disorder of bone, osteogenesis imperfecta. While we documented striking clinical benefit soon after transplantation, the measured level of osteopoietic engraftment was low. To improve the efficacy of BMT for bone disorders, we sought to gain insight into the cellular mechanism of engraftment of transplantable marrow osteoprogenitors. MATERIALS AND METHODS: We transplanted unfractionated bone marrow harvested from green fluorescent protein-transgenic FVB/N mice into lethally irradiated FVB/N recipients. At 3 weeks posttransplantation, we assessed hematopoietic engraftment by flow cytometry and osteopoietic engraftment by immunohistochemical staining for the green fluorescent protein. RESULTS: We show that engraftment of transplantable marrow osteoprogenitors is saturable with a maximal engraftment of about 15% of all bone cells in the epiphysis and metaphysis of the femur at 3 weeks after transplantation. The number of engrafting sites is not up- or downregulated in response to initial progenitor cell engraftment, and there is no evidence for clonal succession of osteopoietic differentiation of engrafted progenitors. CONCLUSIONS: Our findings indicate that the capacity for initial osteopoietic engraftment after BMT is limited and "megadose" stem cell transplantation is unlikely to enhance engraftment. Thus, novel strategies to foster osteopoietic chimerism must be developed.

Re-training the deaf ear: Auditory training for adult cochlear implant users with singlesided deafness.

Objective: While cochlear implant (CI) provision for adults with single-sided deafness (SSD) is now an accepted treatment option, auditory training programs specific to this group of CI users have not been described. This paper details the auditory training protocol and critical factors required to rehabilitate CI users with post-lingual SSD. Outcomes and Results: Several key factors are integral to the success of the rehabilitation program; these include 1) CI users with SSD require a map that is balanced as closely as possible to their normal hearing ear and has optimal mapping levels; 2) the auditory training program needs to be stimulating, rewarding, and directly stimulate the implanted ear via Direct Auditory Input (DAI); 3) CI users need to achieve some success in the early post-implantation stages to maintain or increase their motivation; 3) CI users need to be fully committed to the auditory training; and 5) a well-defined structured auditory training program with immediate feedback and markers of success helps ensure optimal communication outcomes. As an indication of success, from the foundation of the program in 2008 until the present all adults with SSD who have received a CI at our clinic (N = 114) only 5 have elected to stop using their device. Conclusion: The auditory training program described herein has been developed to optimize hearing and quality of life outcomes for adult CI users with SSD.

Year-Long Rhinovirus Infection is Influenced by Atmospheric Conditions, Outdoor Air Virus Presence, and Immune System-Related Genetic Polymorphisms.

Rhinovirus is a common picornavirus with over 150 serotypes and three species, which is responsible for half of the human common cold cases. In people with chronic respiratory conditions and elders, it may also cause life-threatening diseases. Transmission routes are not definitively established but may involve direct human-to-human and indirect transmission (surfaces and aerosols based). In the present study, year-long presence of virus was tested by qPCR in the nostrils of young healthy volunteers and indoor and outdoor air samples. Results were correlated to atmospheric conditions (meteorological and air quality parameters) and voluntaries immune system-related genetic polymorphisms (TOLLIP rs5743899, IL6 rs1800795, IL1B rs16944, TNFA rs1800629) typed by PCR-RFLP. Nasal samples showed increased frequency and viral titers of Rhinovirus in spring and autumn. No indoor air samples tested positive for Rhinovirus, whereas outdoor air samples tested positive in late autumn. Sun radiation, atmospheric SO2, and benzene levels correlated with nostrils Rhinovirus detection. Both IL6 and TOLLIP polymorphisms but not TNFA or IL1B influenced Rhinovirus detection in the nostrils of voluntaries. Taken together, the results indicate that Rhinovirus circulation is determined by environmental conditions (weather, air-borne virus, and air pollution) and genetically encoded individual variation in immunity.