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.

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.

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.

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.

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.

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.

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.

The prognostic significance of the lymph node ratio in oral cancer differs for anatomical subsites.

The aim of this study was to validate the prognostic significance of the lymph node ratio (LNR) in patients suffering from oral squamous cell carcinoma in regard to different anatomical subsites. A cohort of 430 patients was investigated to determine the rates of primary metastasis and local and regional disease recurrence. Correlation analysis of the LNR with relevant clinical and pathological parameters was performed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the prognostic impact for different subsites. Significantly differing rates of primary metastasis and loco-regional disease recurrence were found for cancer of different anatomical subsites of the head and neck. Furthermore, ROC curve analysis suggested that LNR has prognostic relevance in subsets of cancer (tongue, P< 0.001; alveolar process, P= 0.04; maxilla, P= 0.03; buccal mucosa, P= 0.02). The LNR of cancer located in the soft palate (P= 0.6) and floor of the mouth (P= 0.11) showed little or no association with the clinical outcome. There is the need for a more sensitive consideration of the LNR as a factor in the assessment of risk and the treatment decision, as the anatomical subsite plays a crucial role in its impact on the clinical outcome.

Molecular Epidemiology of Noninvasive and Invasive Group A Streptococcal Infections in Cape Town.

Group A streptococcus (GAS) is responsible for a wide range of noninvasive group A streptococcal (non-iGAS) and invasive group A streptococcal (iGAS) infections. Information about the emm type variants of the M protein causing GAS disease is important to assess potential vaccine coverage of a 30-valent vaccine under development, particularly with respect to how they compare and contrast with non-iGAS isolates, especially in regions with a high burden of GAS. We conducted a prospective passive surveillance study of samples from patients attending public health facilities in Cape Town, South Africa. We documented demographic data and clinical presentation. emm typing was conducted using CDC protocols. GAS was commonly isolated from pus swabs, blood, deep tissue, and aspirates. Clinical presentations included wound infections (20%), bacteremia (15%), abscesses (9%), and septic arthritis (8%). Forty-six different emm types were identified, including M76 (16%), M81 (10%), M80 (6%), M43 (6%), and M183 (6%), and the emm types were almost evenly distributed between non-iGAS and iGAS isolates. There was a statistically significant association with M80 in patients presenting with noninvasive abscesses. Compared to the 30-valent vaccine under development, the levels of potential vaccine coverage for non-iGAS and iGAS infection were 60% and 58%, respectively, notably lower than the coverage in developed countries; five of the most prevalent emm types, M76, M81, M80, M43, and M183, were not included. The emm types from GAS isolated from patients with invasive disease did not differ significantly from those from noninvasive disease cases. There is low coverage of the multivalent M protein vaccine in our setting, emphasizing the need to reformulate the vaccine to improve coverage in areas where the burden of disease is high.IMPORTANCE The development of a vaccine for group A streptococcus (GAS) is of paramount importance given that GAS infections cause more than 500,000 deaths annually across the world. This prospective passive surveillance laboratory study evaluated the potential coverage of the M protein-based vaccine currently under development. While a number of GAS strains isolated from this sub-Sahara African study were included in the current vaccine formulation, we nevertheless report that potential vaccine coverage for GAS infection in our setting was approximately 60%, with four of the most prevalent strains not included. This research emphasizes the need to reformulate the vaccine to improve coverage in areas where the burden of disease is high.

Relations between mandible-only advancement surgery, the extent of the posterior airway space, and the position of the hyoid bone in Class II patients: a three-dimensional analysis.

The objective of the present study was to evaluate the relation between mandibular advancement, the three-dimensional extent of the posterior airway space (PAS), and the position of the hyoid bone, using cone-beam computed tomography (CT). Twenty-eight Class II patients (21 women (mean (SD) age 29 (9) years) and seven men (mean (SD) age 23 (6) years)), who had had mandibular-only advancement surgery (Obwegeser-Dal Pont) were included in the study. In each case, cone-beam CT scans were taken one week before and six months after operation, and a retrospective analysis made of the alterations of several airway variables (volume, mean cross-sectional area, and diameter) and the three-dimensional extent of mandibular and hyoid movement, by using IPlan® cranial software. A linear regression was also done to correlate mandibular advancement, the movement of the hyoid bone, and airway variables. There were significant postoperative increases in all volumetric PAS variables, and in most diametric and spherical variables (p<0.05). There was also a significant linear relation between forward displacement of the mandible and the movement of the hyoid bone (p<0.05). These results show that mandible-only advancement surgery causes an increase in most dimensions of the PAS. This intervention can be assumed to reduce airway resistance and therefore might be a suitable treatment option for patients with obstructive sleep apnoea syndrome.

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.

Long-term donor site morbidity in head and neck cancer patients and its impact on quality of life: a cross-sectional study.

Modern head and neck reconstructive surgery offers a multitude of different reconstructive options. In such cases, donor site morbidity is an important factor in the affected patient's decision-making. The aim of this study was to perform an objective comparison of donor site morbidity for the five most frequent microvascular donor sites in head and neck reconstructive surgery (radial forearm, anterolateral thigh, fibula, iliac crest, and scapula) using a uniform testing system. In this cross-sectional study, 117 donor sites were analyzed (106 for malignant disease and 11 for non-malignant disease): 73 radial forearm, 14 scapula, 12 anterolateral thigh, 10 fibula, and eight iliac crest. Testing consisted of range of motion, muscle strength, and sensation. The non-affected side served as the control. Quality of life was assessed using the Washington Quality of Life Questionnaire version 4 in its German translation. Range of motion was restricted in 15 cases (12.8%). Muscle strength was decreased in 58 cases (49.6%). Sensation was reduced in 70 cases (60%). Concerning quality of life, 31.2% of patients were limited in their daily activities. The scapula flap showed the highest incidence of overall donor site morbidity. However, correlation between objective and subjective donor site impairment was weak and the majority of patients experienced only minor limitations.

Niche Partitioning in Theropod Dinosaurs: Diet and Habitat Preference in Predators from the Uppermost Cedar Mountain Formation (Utah, U.S.A.).

We explore hypothetical ecologies to explain diversity among predatory dinosaurs in North America's medial Cretaceous, based on occurrence, tooth morphology, and stable isotope analysis. The Mussentuchit local fauna, Utah, USA, is among the best-known terrestrial vertebrate assemblages from the Cretaceous. Study samples include teeth from six microvertebrate sites, ranging in depositional setting from distal floodplain to channel lags. We recognize four theropod morphotypes: a comparatively large theropod (morph 1), a medium-sized dromaeosaurid (morph 2), a small dromaeosaurid (morph 3), and a tooth-morph similar to the genus Richardoestesia (morph 4). These four morphotypes vary significantly in mean size, from 15.1 mm in the largest theropod to 3.7 mm in Richardoestesia. Further, tooth representation from two of the best-sampled microsites (representing a channel/splay and floodplain deposit) show differing patterns of abundances with morphs 1 and 3 having roughly the same abundance in both sites, while morph 2 was more abundant in the floodplain setting and morph 4 was more abundant in the channel/splay. Stable isotope analysis (δ13C; δ18O) of tooth carbonate from the theropod morphotypes, goniopholidid crocodilians, and matrix (to test for diagenesis) from these sites were also analyzed. The theropods show modest differences in δ13C values between each other, with carbonate from the teeth of morphs 1, 3, and 4 being enriched in 13C for the channel/splay relative to the floodplain environments, possibly indicative of dietary plasticity in these species. We hypothesize that these data indicate that the Mussentuchit theropods had different niches within the predator guild, suggesting plausible means by which ecospace was divided among the predatory dinosaurs of the Mussentuchit local fauna.

MetaMap: an atlas of metatranscriptomic reads in human disease-related RNA-seq data.

Background: With the advent of the age of big data in bioinformatics, large volumes of data and high-performance computing power enable researchers to perform re-analyses of publicly available datasets at an unprecedented scale. Ever more studies imply the microbiome in both normal human physiology and a wide range of diseases. RNA sequencing technology (RNA-seq) is commonly used to infer global eukaryotic gene expression patterns under defined conditions, including human disease-related contexts; however, its generic nature also enables the detection of microbial and viral transcripts. Findings: We developed a bioinformatic pipeline to screen existing human RNA-seq datasets for the presence of microbial and viral reads by re-inspecting the non-human-mapping read fraction. We validated this approach by recapitulating outcomes from six independent, controlled infection experiments of cell line models and compared them with an alternative metatranscriptomic mapping strategy. We then applied the pipeline to close to 150 terabytes of publicly available raw RNA-seq data from more than 17,000 samples from more than 400 studies relevant to human disease using state-of-the-art high-performance computing systems. The resulting data from this large-scale re-analysis are made available in the presented MetaMap resource. Conclusions: Our results demonstrate that common human RNA-seq data, including those archived in public repositories, might contain valuable information to correlate microbial and viral detection patterns with diverse diseases. The presented MetaMap database thus provides a rich resource for hypothesis generation toward the role of the microbiome in human disease. Additionally, codes to process new datasets and perform statistical analyses are made available.

Participation in research improves overall patient management: insights from the Global Rheumatic Heart Disease registry (REMEDY).

BACKGROUND: Rheumatic heart disease (RHD) is a major public health problem in low- and middle-income countries (LIMCs), with a paucity of high-quality trial data to improve patient outcomes. Investigators felt that involvement in a recent large, observational RHD study impacted positively on their practice, but this was poorly defined. AIM: The purpose of this study was to document the experience of investigators and research team members from LMICs who participated in a prospective, multi-centre study, the global Rheumatic Heart Disease Registry (REMEDY), conducted in 25 centres in 14 countries from 2010 to 2012. METHOD: We conducted an online survey of site personnel to identify and quantify their experiences. Telephone interviews were conducted with a subset of respondents to gather additional qualitative data. We asked about their experiences, positive and negative, and about any changes in RHD management practices resulting from their participation in REMEDY as a registry site. RESULTS: The majority of respondents in both the survey and telephone interviews indicated that participation as a registry site improved their management of RHD patients. Administrative changes included increased attention to follow-up appointments and details in patient records. Clinical changes included increased use of penicillin prophylaxis, and more frequent INR monitoring and contraceptive counselling. CONCLUSION: Our study demonstrates that participation in clinical research on RHD can have a positive impact on patient management. Furthermore, REMEDY has led to increased patient awareness and improved healthcare workers' knowledge and efficiency in caring for RHD patients.