The etiological evaluation of sensorineural hearing loss in children.

This study aims to evaluate the etiology of pediatric sensorineural hearing loss (SNHL). A total of 423 children with SNHL were evaluated, with the focus on the determination of causative genetic and acquired etiologies of uni- and bilateral SNHL in relation to age at diagnosis and severity of the hearing loss. We found that a stepwise diagnostic approach comprising of imaging, genetic, and/or pediatric evaluation identified a cause for SNHL in 67% of the children. The most common causative finding in children with bilateral SNHL was causative gene variants (26%), and in children with unilateral SNHL, a structural anomaly of the temporal bone (27%). The probability of finding an etiologic diagnosis is significantly higher in children under the age of 1 year and children with profound SNHL.Conclusions: With our stepwise diagnostic approach, we found a diagnostic yield of 67%. Bilateral SNHL often has a genetic cause, whereas in unilateral SNHL structural abnormalities of the labyrinth are the dominant etiologic factor. The diagnostic yield is associated with the age at detection and severity of hearing loss: the highest proportion of causative abnormalities is found in children with a young age at detection or a profound hearing loss. What is Known: • Congenital sensorineural hearing loss is one of the most common congenital disorders • Determination of the cause is important for adequate management and prognosis and may include radiology, serology, and DNA analysis What is New: • Using a stepwise diagnostic approach, causative abnormalities are found in 67% both in uni- and bilateral SNHL, with the highest diagnostic yield in very young children and those suffering from profound hearing loss • Bilateral SNHL often has a genetic cause, whereas in unilateral SNHL structural abnormalities of the labyrinth are the dominant etiologic factor.

Environmental and mucosal microbiota and their role in childhood asthma.

BACKGROUND: High microbial diversity in the environment has been associated with lower asthma risk, particularly in children exposed to farming. It remains unclear whether this effect operates through an altered microbiome of the mucosal surfaces of the airways. METHODS: DNA from mattress dust and nasal samples of 86 school age children was analyzed by 454 pyrosequencing of the 16S rRNA gene fragments. Based on operational taxonomic units (OTUs), bacterial diversity and composition were related to farm exposure and asthma status. RESULTS: Farm exposure was positively associated with bacterial diversity in mattress dust samples as determined by richness (P = 8.1 × 10-6 ) and Shannon index (P = 1.3 × 10-5 ). Despite considerable agreement of richness between mattress and nasal samples, the association of richness with farming in nasal samples was restricted to a high gradient of farm exposure, that is, exposure to cows and straw vs no exposure at all. In mattress dust, the genera Clostridium, Facklamia, an unclassified genus within the family of Ruminococcaceae, and six OTUs were positively associated with farming. Asthma was inversely associated with richness [aOR = 0.48 (0.22-1.02)] and Shannon index [aOR = 0.41 (0.21-0.83)] in mattress dust and to a lower extent in nasal samples [richness aOR 0.63 = (0.38-1.06), Shannon index aOR = 0.66 (0.39-1.12)]. CONCLUSION: The stronger inverse association of asthma with bacterial diversity in mattress dust as compared to nasal samples suggests microbial involvement beyond mere colonization of the upper airways. Whether inhalation of metabolites of environmental bacteria contributes to this phenomenon should be the focus of future research.

A tailored implementation strategy to reduce the duration of intravenous antibiotic treatment in community-acquired pneumonia: a controlled before-and-after study.

We previously showed that 40 % of clinically stable patients hospitalised for community-acquired pneumonia (CAP) are not switched to oral therapy in a timely fashion because of physicians' barriers. We aimed to decrease this proportion by implementing a novel protocol. In a multi-centre controlled before-and-after study, we evaluated the effect of an implementation strategy tailored to previously identified barriers to an early switch. In three Dutch hospitals, a protocol dictating a timely switch strategy was implemented using educational sessions, pocket reminders and active involvement of nursing staff. Primary outcomes were the proportion of patients switched timely and the duration of intravenous antibiotic therapy. Length of hospital stay (LOS), patient outcome, education effects 6 months after implementation and implementation costs were secondary outcomes. Statistical analysis was performed using mixed-effects models. Prior to implementation, 146 patients were included and, after implementation, 213 patients were included. The case mix was comparable. The implementation did not change the proportion of patients switched on time (66 %). The median duration of intravenous antibiotic administration decreased from 4 days [interquartile range (IQR) 2-5] to 3 days (IQR 2-4), a decrease of 21 % [95 % confidence interval (CI) 11 %; 30 %) in the multi-variable analysis. LOS and patient outcome were comparable before and after implementation. Forty-three percent (56/129) of physicians attended the educational sessions. After 6 months, 24 % (10/42) of the interviewed attendees remembered the protocol's main message. Cumulative implementation costs were 5,798 (20/reduced intravenous treatment day). An implementation strategy tailored to previously identified barriers reduced the duration of intravenous antibiotic administration in hospitalised CAP patients by 1 day, at minimal cost.

Electroluminescence in single layer MoS2.

We detect electroluminescence in single layer molybdenum disulfide (MoS2) field-effect transistors built on transparent glass substrates. By comparing the absorption, photoluminescence, and electroluminescence of the same MoS2 layer, we find that they all involve the same excited state at 1.8 eV. The electroluminescence has pronounced threshold behavior and is localized at the contacts. The results show that single layer MoS2, a direct band gap semiconductor, could be promising for novel optoelectronic devices, such as two-dimensional light detectors and emitters.

Positive urinary antigen tests for Streptococcus pneumoniae in community-acquired pneumonia: a 7-year retrospective evaluation of health care cost and treatment consequences.

A positive pneumococcal urinary antigen test (PUAT) for Streptococcus pneumoniae allows an early switch from empiric to targeted treatment in hospitalised community-acquired pneumonia (CAP) patients. The economic and treatment consequences of this widespread implemented test are, however, unknown. We retrospectively evaluated all tests performed since its introduction in two teaching hospitals. Data on patient characteristics, treatment, admission and outcome were retrieved from the electronic patient files. Test benefits were expressed as the number of days that targeted therapy (i.e. penicillin) was administered to hospitalised CAP patients due to a positive PUAT. This calculation was based on the timing of the PUAT and the initiation of targeted therapy. Subsequently, we performed two direct cost analyses from a hospital perspective, first including tests performed for CAP only, and second including costs of all (excessive) tests. Between 2005 and 2012, 3,479 PUATs were performed, of which 1,907 (55 %) were for CAP. A total of 1,638 PUATs (86 %) were negative and 269 (14 %) were positive. Fifty-two (19 %) positive tests were excluded. In 75 (35 %) of the 217 remaining positive tests, a positive PUAT led to targeted treatment during 293 cumulative admission days. Testing costs for CAP only were €131 per targeted treatment day. These costs were €257 if local protocol dictated PUAT use for all CAP cases, as opposed to €72 if the test was reserved for severe cases only. When including all tests, PUAT costs were €254 per targeted treatment day. Therefore, improving the selective use of the PUAT in hospitalised CAP patients may lead to increased (cost-)efficiency.

[Therapeutic strategies for the reconstruction of extensive mandibular defects]. / Behandlungskonzepte zur Rekonstruktion bei ausgedehnten Unterkieferdefekten.

Tumours of the mandibular bone or adjacent soft tissue often necessitate mandibular resection. Subsequent primary bone reconstruction to achieve optimal functional and aesthetic results has been made possible by microvascular surgical techniques and now represents the international gold standard. Microvascular reanastomosis of autologous bone grafts from the iliac crest or fibula is the most common procedure for reconstruction of the mandible. The localisation and extent of the expected defect, as well as a patient's overall condition and ability to tolerate long surgical procedures must be carefully considered before deciding upon the course of treatment. Additional microvascular reanastomosis of soft tissue flaps and stereolithographic models facilitate preoperative planning and broaden the surgical spectrum. Following successful reconstruction of the bone, insertion of dental implants and prosthetic rebuilding are required to complete rehabilitation, including restoration of the patient's ability to chew and speak. The authors recommend specialised oncologic centres for such complex surgical reconstructions.

Chiari malformation in nonsyndromal single craniosynostosis--much ado about nothing?

BACKGROUND: The significance of Chiari malformation in nonsyndromal-isolated craniosynostosis is still not well documented. Hence, in the present study we investigated the incidence of Chiari malformation in a larger series of patients with nonsyndromic-isolated single-suture craniosynostosis over a 9-year period using preoperative magnetic resonance imaging (MRI). METHODS: Of 215 children who had undergone surgery for nonsyndromic-isolated craniosynostosis, 89 cases (41.4 %) had MRI prior to surgery. All MRIs were screened for Chiari malformation. RESULTS: Only one patient (1.1 %) with isolated lambdoid synostosis showed Chiari malformation preoperatively, which was defined as a cerebellar tonsillar descent greater than 5 mm below the foramen magnum. However, no clinical symptoms were associated with Chiari malformation in this patient. CONCLUSIONS: As Chiari malformation is more likely to be associated with syndromic craniosynostosis, nonsyndromic bilateral coronal synostosis, or synostosis of the lambdoid suture, a general use of MRI as a screening tool for Chiari malformation should not be recommended for patients with nonsyndromic-isolated craniosynostosis who lack clinical symptoms.

Photogrammetric evaluation of corrective surgery for trigonocephaly.

The aim of this study was to capture preoperative, postoperative, and follow-up head shapes of male trigonocephaly patients who underwent fronto-orbital remodelling (FOR), using three-dimensional (3D) photography. Fifty-seven male infants with metopic synostosis operated on using standardized FOR during a 5-year period were included. All measurements were compared with those of an age-matched healthy control cohort (n = 253 for early postoperative comparison, n = 43 for the 1-year follow-up comparison) to determine the effect of FOR at 14 days and at 1 year post-surgery. Intracranial volume, frontal angle, nasofrontal angle, interfrontoparietal-interparietal ratio, and inter-orbital distances were measured 1 day preoperatively, 14 days and 1 year postoperatively. Mean age at surgery was 9.7 ± 1.1 months. Prior to surgery, boys with metopic synostosis showed a reduced intracranial volume (-7.0%, P < 0.001), frontal angle (-10.2%, P < 0.001), interfrontoparietal-interparietal ratio (-4.9%, P < 0.01), and orbital distances (-6.5%, P < 0.001) compared to the reference group, but values did not differ significantly from the specific control group after surgery (all P> 0.05). This was consistent by the time of the follow-up examination. Corrective surgery should therefore aim to achieve volume expansion and correction of the deformity. Furthermore, 3D photogrammetry provides a valuable alternative to computed tomography scans in the diagnosis of metopic synostosis, significantly reducing the amount of radiation exposure to the brain.

A novel approach to the study of hypoxia-ischemia-induced clinical and subclinical seizures in the neonatal rat.

Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of acute mortality and chronic neurologic morbidity in infants and children. HIE is the most common cause of neonatal seizures, and seizure activity in neonates can be clinical, with both EEG and behavioral symptoms, subclinical with only EEG activity, or just behavioral. The accurate detection of these different seizure manifestations and the extent to which they differ in their effects on the neonatal brain continues to be a concern in neonatal medicine. Most experimental studies of the interaction between hypoxia-ischemia (HI) and seizures have utilized a chemical induction of seizures, which may be less clinically relevant. Here, we expanded our model of unilateral cerebral HI in the immature rat to include video EEG and electromyographic recording before, during and after HI in term-equivalent postnatal-day-12 rats. We observed that immature rats display both clinical and subclinical seizures during the period of HI, and that the total number of seizures and time to first seizure correlate with the extent of tissue damage. We also tested the feasibility of developing an automated seizure detection algorithm for the unbiased detection and characterization of the different types of seizure activity observed in this model.

An appraisal of laboratory models of androgenetic alopecia: A systematic review.

Background: Androgenetic alopecia (AGA) is the most common form of non-scarring alopecia in humans. Several studies have used different laboratory models to study the pathogenesis and interventions for AGA. These study models have proved beneficial and have led to the approval of two drugs. However, the need to build on existing knowledge remains by examining the relevance of study models to the disease. Objective: We sought to appraise laboratory or pre-clinical models of AGA. Method: We searched through databases (PubMed, ScienceDirect, Web of Science, World CAT, Scopus and Google Scholar) for articles on AGA-related studies from 1942 to March 2019 with a focus on study models. Results: The search rendered 101 studies after screening and deduplication. Several studies (70) used in vitro models, mostly consisting of two-dimensional monolayer cells for experiments involving the characterization of androgen and 5-alpha reductase (5AR) and inhibition thereof, the effects of dihydrotestosterone (DHT) and biomarker(s) of AGA. Twenty-seven studies used in vivo models of mice and monkeys to investigate DHT synthesis, the expression and inhibition of 5AR and hair growth. Only four studies used AGA-related or healthy excisional/punch biopsy explants as ex vivo models to study the action of 5AR inhibitors and AGA-associated genes. No study used three-dimensional [3-D] organoids or organotypic human skin culture models. Conclusion: We recommend clinically relevant laboratory models like human or patient-derived 3-D organoids or organotypic skin in AGA-related studies. These models are closer to human scalp tissue and minimize the use of laboratory animals and could ultimately facilitate novel therapeutics.

Menthacarin induces calcium ion influx in sensory neurons, macrophages and colonic organoids of mice.

AIMS: Menthacarin is a herbal combination that is clinically used for the treatment of functional gastrointestinal disorders (FGIDs). In several clinical studies, Menthacarin reduced visceral hypersensitivity-related symptoms. Pathogenesis of visceral hypersensitivity is multifactorial. This involves several cell types and different transient receptor potential ion channels (TRPs); these ion channels are highly conductive for calcium ions. Since transient changes in cytosolic calcium levels are crucial for many functions of living cells, we investigated if Menthacarin can induce calcium influx in sensory, largely nociceptive, neurons from dorsal root ganglia (DRG), peritoneal macrophages (PMs) and colonic organoids. MAIN METHODS: We employed the calcium imaging technique on sensory neurons from DRG, PMs and colonic organoids isolated from mice. All cells were superfused by Menthacarin at several concentrations (600, 1200, 1800 µg/ml) during the experiments, followed by calcium ionophor ionomycin (Iono., 1 µM) as a positive control. KEY FINDINGS: Menthacarin induced concentration-dependent calcium ion influx in all investigated cell types. Furthermore, repeated applications of Menthacarin induced tachyphylaxis (desensitisation) of calcium responses in sensory neurons and colonic organoids. SIGNIFICANCE: Menthacarin-induced calcium influx into sensory neurons, macrophages and colonic organoids is probably related to its clinical desensitising effects in patients with FGIDs.

Neck involvement and disease recurrence in adenoid cystic carcinoma of the minor salivary glands: the role of surgery in primary and progressive disease.

The aim of this study was to analyse the rates of metastatic events and clinical outcomes of patients with adenoid cystic carcinoma (ACC) of the minor salivary glands and to critically evaluate the role of surgical therapy. A retrospective cohort study was designed including all patients with ACC of the oral minor salivary glands treated in the study department during the years 2010-2017. Relevant clinicopathological data were analysed to determine factors with an impact on overall survival (OS) and progression-free survival (PFS). Forty-one patients with primary ACC of the oral cavity and the oropharynx were included. Cervical metastases were found in 14 patients (34.1%) and were shown to have a significant negative impact on OS (P=0.009) and PFS (P=0.03). Sixteen patients developed disease recurrence during follow-up (39.0%) and most patients exhibited local disease recurrence with or without regional or distant metastases (14/16, 87.5%). Local recurrence was treated successfully with surgery in five cases. We recommend surgical therapy for patients with ACC of the minor salivary glands, including elective neck dissection and microvascular reconstruction, to optimize the planning of adjuvant therapy.

Management and outcome of middle ear adenomatous neuroendocrine tumours: A systematic review.

Middle ear adenomatous neuroendocrine tumours (MEANTs) are rare, unpredictable tumours. Although most MEANTs are characterized by a benign biological behaviour and indolent growth pattern, some studies have reported locally invasive and metastastic disease. Currently, the optimal management strategy for MEANTs remains subject of debate. The aim of this study is to review the literature on MEANTs with focus on its clinical characteristics, treatment strategies and outcome. A systematic review was conducted using PubMed, Embase and Cochrane databases. A total of 111 studies comprising 198 patients with MEANT were included. Treatment modalities comprised surgery (90%), surgery with adjuvant radiotherapy (9%) and palliative (chemo)radiotherapy in (1%). Local recurrence was observed in 25% of the patients and 7% of the patients developed metastasis, over a median period of 5.7 years (range 7 months - 32 years). Twelve of 13 patients (92%) who developed metastases had a local recurrence. Four patients (2%) died of MEANT: three due to distant metastases and one due to extensive local recurrence. Reliable histopathologic predictors of outcome could not be identified. These findings indicate that the clinical presentations of MEANT vary substantially, the overall recurrence rate is considerable and initial local tumour control is paramount. Because of the unpredictable clinical course, prolonged follow-up is warranted.

In situ small angle x-ray scattering measurements of the filling process of polyisobutylene and poly-epsilon-caprolactone in ion track etched polycarbonate nanopores.

We present results of in situ measurements of the filling process of polymer melts in nanopores. After accurate characterization of the empty nanopores, they are filled with the hydrophobic polyisobutylene and the hydrophilic poly-epsilon-caprolactone. The filling process is investigated in situ with small angle x-ray scattering. The time-dependent scattering intensity is investigated with a model function based on the Lucas-Washburn equation for the filling process of liquids in cylindrical pores. The model function describes the data qualitatively well in terms of a t-dependency of the filling height, but deviates clearly from the expected quantitative values of the bulk material properties. Furthermore, the occurrence of a precursor film wetting the nanopore surface on a short time scale is observed.

Spatio-temporal analysis of the risk of depression at district-level and association with greenness based on the Heinz Nixdorf Recall Study.

In urban health studies where spatial and temporal changes are of importance, spatio-temporal variations are usually neglected. For the Heinz Nixdorf Recall Study, we investigate spatio-temporal variation in analyses of effects of urban greenness on depression by including spatio-temporal random effect terms in a Poisson model on district level. Our results show negative associations between greenness and depression. The findings suggest strong temporal autocorrelation and weak spatial effects. Even if the weak spatial effects are suggestive of neglecting them, as in our case, spatio-temporal random effects should be taken into account to provide reliable inference in urban health studies.

Topographic bone thickness maps to evaluate the intuitive placement of titanium miniplates for nasal prostheses.

The aim of this study was to evaluate the intuitive placement of titanium miniplates. The hypothesis was that virtual planning can improve miniplate placement. Twenty patients were included in the study. These patients were fitted with 21 titanium miniplates (16 y-plates, three t-plates, and two u-plates) to retain nasal prostheses between 2005 and 2017. Colour-coded topographic bone thickness maps (TBTMs) were created in fused pre- and postoperative computed tomography. Implants were virtually transposed at the position of highest bone thickness. The bone thickness index (BTI) was calculated as the sum of points assigned at each screw (1 point per millimetre up to 4 mm, and 5 points for greater values) divided by the number of screws. One plate broke after 2.8 years, thus plate survival after 5 years was 91% using the Kaplan-Meier method. The BTI for all 21 plates increased from 3.4 to 4.1 points using virtual transposition (P<0.001). No significant changes were observed in t- and u-plates, but the median BTI increased from 3.1 to 4.1 points (P<0.0005) in 16 y-plates. The change was substantial (≥0.5 points) in 9/16 y-plates. Therefore, the hypothesis that virtual planning improves implant placement was accepted.

Dual opposing actions of STW 5 on TRP receptors mediate neuronal desensitisation in vitro.

AIMS: STW 5 is an herbal drug combination used for the treatment of functional gastrointestinal disorders (FGIDs) with visceral hypersensitivity as the therapy-resistant hallmark. STW 5 has been clinically proven to alleviate visceral hypersensitivity-related symptoms, including abdominal pain, bloating, nausea, and early satiety. However, the molecular and cellular mechanisms underlying the antinociceptive action of STW 5 remain unknown. Here, we investigate the role of STW 5 in the calcium mobilisation of dorsal root ganglion (DRG) sensory neurons. MAIN METHODS: Calcium imaging experiments were performed with freshly dissociated cultured murine DRG neurons isolated from mice by microfluorometry. TRPA1-deficient DRGs, TRPV1-deficient DRGs, TRPA1/V1 double-deficient DRGs, and wild-type DRGs have been used to investigate the role of TRPs ion channels in mediating STW 5 action. KEY FINDINGS: STW 5 (1.74 and 5.8 mg/ml) induced calcium ion influx into DRG neurons in a concentration-dependent manner. Calcium transients were desensitised during repeated exposure to STW 5, an effect that was facilitated in TRPA1-deficient DRGs and less pronounced in TRPV1-deficient DRGs compared to wild-type (WT) DRGs. SIGNIFICANCE: Repeated exposure to STW 5 induced desensitisation of sensory neurons and may ultimately contribute to its proven clinical efficacy against sensory-related symptoms in patients with FGID, including abdominal pain, bloating, nausea, and early satiety. This effect is modulated by the two prominent irritant sensors in nociceptors, TRPA1 and TRPV1.