The Trotter collection: A review of Mildred Trotter's hair research and an update for studies of human variation.

OBJECTIVES: Mildred Trotter was an anatomist and physical anthropologist whose studies on hair morphology, growth, somatic distribution, and trait relationships to age and ethnogeographic population were foundational to the field of microscopical hair analysis. The collection of human hair samples she assembled for her research has been an underutilized resource for studies on human hair variation. We applied updated methods and reviewed Trotter's original data to reassess the relationship hair traits have to diverse population labels. METHODS: Hair form and pigmentation patterns were measured from a subset of the hair samples accumulated by Trotter and we compared our data to Trotter's original results. Variability in hair traits were tested within individuals, within populations, and among ethnogeographic groups. RESULTS: Measured hair cross-section dimensions and melanosome density and distribution revealed substantial variability within individuals and ethnogeographic populations. Hair traits were found to not be distinctly separable by ancestry but instead showed continuous variation across human populations. Trotter's measurements were precise and the dataset she compiled remains valid, though the conclusions should be reviewed in light of our current understanding of human variation. DISCUSSION: Our findings support moving away from categorical ancestry classifications and eliminating the use of outdated racial typologies in favor of more descriptive trait analysis. Detailed analysis of trait pattern distributions are presented that may be useful for future research on human variation. We point to the need for additional research on human variation and hair trait relationships with reference to known population affinity.

Impact of Physiological Fluctuations of Sex Hormones During the Menstrual Cycle on Glucose Metabolism and the Gut Microbiota.

Diabetes mellitus is one of the most prevalent chronic diseases. Previous studies have shown differences in glucose metabolism between males and females. Moreover, difficulties in medication adherence have been reported in females with type 2 diabetes. These observations are believed to be caused by fluctuations in sex hormone concentrations during the menstrual cycle. Furthermore, gut microbiota is linked to female host metabolism and sex hormone production. Understanding the interactions between fluctuating hormone concentrations during the menstrual cycle, gut microbiota, and glucose metabolism in humans is significant because of the increasing prevalence of diabetes and the consequent need to expand preventive efforts. A literature search was performed to determine and summarize the existing evidence, deduce future research needs to maintain female health, and investigate the relationship between the physiological menstrual cycle and glucose metabolism. Studies from 1967 to 2020 have already examined the relationship between variations during the menstrual cycle and glucose metabolism in healthy female subjects using an oral-glucose tolerance test or intravenous glucose tolerance test. However, the overall number of studies is rather small and the results are contradictory, as some studies detected differences in glucose concentrations depending on the different cycle phases, whereas others did not. Some studies reported lower glucose levels in the follicular phase than in the luteal phase, whereas another study detected the opposite. Data on gut microbiota in relation to the menstrual cycle are limited. Conflicting results exist when examining the effect of hormonal contraceptives on the gut microbiota and changes in the course of the menstrual cycle. The results indicate that the menstrual cycle, especially fluctuating sex hormones, might impact the gut microbiota composition.The menstrual cycle may affect the gut microbiota composition and glucose metabolism. These results indicate that glucose tolerance may be the greatest in the follicular phase; however, further well-conducted studies are needed to support this assumption.

Middle ear cholesteatoma in two cats diagnosed with the aid of video-otoscopy.

Case series summary: The present report describes middle ear cholesteatoma in two cats and also the use of video-otoscopy and flushing to assist with the diagnosis. CT and video-otoscopic examination and flushing were performed in two cats, a 13-year-old mixed breed spayed female cat and a 1-year-old mixed breed male cat, with middle ear cholesteatomas. During the procedure, keratinous material from the middle ears was collected for histopathological evaluation, demonstrating findings consistent with cholesteatoma, and the middle ears were flushed extensively. Relevance and novel information: There is little information about middle ear cholesteatoma in cats, and to the authors' knowledge, there are no reports in cats investigating the use of video-otoscopy to aid in the diagnosis of aural cholesteatoma, and this report demonstrates that it can aid in the diagnosis of this condition in cats. In addition, one of the cats had a concurrent otic polyp, which has not been previously reported in cats with cholesteatoma. Additionally, this is the first report of cholesteatoma in a young cat. The access to the cholesteatoma material was via ventral bulla osteotomy in one cat and via external canal without video-otoscopy in the other. More information regarding cholesteatoma in cats will help identify potential similarities and differences of this condition in cats compared with humans and dogs.

Breeding from 1891 to 2010 did not increase the content of amylase/trypsin-inhibitors in wheat (Triticum aestivum).

The prevalence of hypersensitivities towards wheat has increased in the last decades. Apart from celiac disease these include allergic and other inflammatory reactions summarized under the term non-celiac wheat sensitivity. One suspected trigger is the family of amylase/trypsin-inhibitors (ATIs), non-gluten proteins that are prominent wheat allergens and that activate the toll-like receptor 4 on intestinal immune cells to promote intestinal and extra-intestinal inflammation. We therefore quantified 13 ATIs in 60 German hexaploid winter wheat cultivars originating from 1891 to 2010 and harvested in three years by targeted liquid chromatography-tandem mass spectrometry combined with stable isotope dilution assay using specific marker peptides as internal standards. The total ATI content and that of the two major ATIs 0.19 and CM3 did not change from old cultivars (first registered from 1891 to 1950) to modern cultivars (1951-2010). There were also no significant changes in ATI distribution.

Local treatment for canine anal sacculitis: A retrospective study of 33 dogs.

BACKGROUND: Little information has been published regarding treatment of canine anal sacculitis (AS). OBJECTIVES: Primary objective: determine the outcomes of AS local treatment at the referral dermatology service of the authors' institution. SECONDARY OBJECTIVE: determine signalment, body condition score (BCS), stool quality and comorbidities associated with AS. ANIMALS: Thirty-three dogs with AS presented to the referral dermatology service between 1 January 2010 and 31 March 2021. MATERIALS AND METHODS: An electronic medical record search was conducted. Information regarding sex, breed, age at disease onset, weight, BCS, stool quality, comorbidities, treatment and treatment outcome were collected. Treatment outcome was categorised as "resolved clinically", "clinical signs resolved per owner", "did not complete treatment" or "failed". Dogs were excluded if seen by another service, not treated for AS, or if perianal sinuses (fistulae), anal sac masses, or anal sac abscesses were identified. RESULTS: Nineteen dogs were male and 14 female. Twenty-four breeds were included. Average age at disease onset was 4.4 years. Average BCS was 5.8 of 9. Stool quality was "poor" in seven of 33 and normal in 23 of 33 cases. Atopic dermatitis was the most common comorbidity (12 of 33). Treatment typically consisted of anal sac flushing with saline followed by infusion using a commercially available steroid/antibiotic/antifungal ointment. Treatment was repeated on average 2.9 times. Resolution of AS was obtained in 24 of 33 cases, clinical signs resolved per owner in four of 33, five of 33 cases did not complete treatment, and no cases failed treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Local treatment with flushing and infusion is effective for treating AS in dogs.

Contexte - Peu d'informations ont été publiées concernant le traitement de la sacculite anale canine (SA). Objectifs - Objectif principal : déterminer les résultats du traitement local de la SA au service de dermatologie des auteurs. Objectif secondaire : déterminer le signalement, le score d'état corporel (BCS), la qualité des selles et les comorbidités associées à la SA. Animaux - Trente-trois chiens SA présentés au service de dermatologie entre le 1er janvier 2010 et le 31 mars 2021. Matériels et méthodes - Une recherche dans le dossier médical électronique a été effectuée. Des informations concernant le sexe, la race, l'âge au début de la maladie, le poids, le BCS, la qualité des selles, les comorbidités, le traitement et les résultats du traitement ont été recueillies. Le résultat du traitement a été classé comme « résolu cliniquement ¼, « signes cliniques résolus par le propriétaire ¼, « n'a pas terminé le traitement ¼ ou « échec ¼. Les chiens ont été exclus s'ils étaient vus par un autre service, non traités pour la SA, ou si des sinus périanaux (fistules), des masses du sac anal ou des abcès du sac anal étaient identifiés. Résultats - Dix-neuf chiens étaient des mâles et 14 des femelles. Vingt-quatre races ont été incluses. L'âge moyen au début de la maladie était de 4,4 ans. Le BCS moyen était de 5,8 sur 9. La qualité des selles était « mauvaise ¼ dans sept cas sur 33 et normale dans 23 cas sur 33. La dermatite atopique était la comorbidité la plus fréquente (12 sur 33). Le traitement consistait généralement en un rinçage du sac anal avec une solution saline suivi d'une perfusion à l'aide d'une pommade stéroïde/antibiotique/antifongique disponible dans le commerce. Le traitement a été répété en moyenne 2,9 fois. La résolution de la SA a été obtenue dans 24 des 33 cas, les signes cliniques ont disparu dans quatre des 33 cas, cinq des 33 cas n'ont pas terminé le traitement et aucun cas n'a échoué au traitement. Conclusions et pertinence clinique - Le traitement local par rinçage et perfusion est efficace pour traiter la SA chez le chien.

Introducción- se ha publicado poca información sobre el tratamiento de la saculitis anal canina (AS). Objetivos - Objetivo primario: determinar los resultados del tratamiento local de la AS en el servicio de referencia dermatológica de la institución de los autores. Objetivo secundario: determinar la presentación clínica, la puntuación de la condición corporal (BCS), la calidad de las heces y las comorbilidades asociadas a la AS. Animales - Treinta y tres perros con AS presentados al servicio de dermatología de referencia entre el 1 de enero de 2010 y el 31 de marzo de 2021. Materiales y métodos - Se realizó una búsqueda en la historia clínica electrónica. Se recopiló información sobre sexo, raza, edad de inicio de la enfermedad, peso, BCS, calidad de las heces, comorbilidades, tratamiento y resultado del tratamiento. El resultado del tratamiento se clasificó como "resuelto clínicamente", "signos clínicos resueltos por propietario", "no completó el tratamiento" o "fracasó". Los perros fueron excluidos si fueron vistos por otro servicio, no tratados por AS, o si se identificaron senos perianales (fístulas), masas en los sacos anales o abscesos en los sacos anales. Resultados- diecinueve perros eran machos y 14 hembras. Se incluyeron veinticuatro razas. La edad promedio de inicio de la enfermedad fue de 4,4 años. BCS promedio fue 5.8 de 9. La calidad de las heces fue "mala" en siete de 33 y normal en 23 de 33 casos. La dermatitis atópica fue la comorbilidad más común (12 de 33). El tratamiento generalmente consistía en enjuagar el saco anal con solución salina seguido de una infusión usando un ungüento de esteroide/antibiótico/antifúngico disponible en el mercado. El tratamiento se repitió un promedio de 2,9 veces. La resolución de AS se obtuvo en 24 de 33 casos, los signos clínicos se resolvieron por propietario en cuatro de 33, cinco de 33 casos no completaron el tratamiento y ningún caso fracasó en el tratamiento. Conclusiones y relevancia clínica- el tratamiento local con lavado e infusión intrasacular es eficaz para tratar la AS en perros.

Contexto - Poucas informações foram publicadas sobre o tratamento da saculite anal (SA) canina. Objetivos - Objetivo primário: determinar os desfechos do tratamento tópico localizado da SA em um serviço especializado de dermatologia veterinária da instituição do autor. Objetivo secundário: determinar as manifestações clínicas, escore de condição corporal (ECC), qualidade das fezes e comorbidades associadas à SA. Animais - Trinta e três cães com SA apresentados ao serviço de dermatologia entre 1° de janeiro de 2010 e 39 de março de 2021. Materiais e métodos - Realizou-se um levantamento de prontuários eletrônicos. Foram coletadas informações sobre sexo, raça, idade no surgimento da doença, peso, ECC, qualidade das fezes, comorbidades, tratamentos e desfecho do tratamento. O desfecho do tratamento foi categorizado como "resolvido clinicamente", "sinais clínicos resolvidos de acordo com o tutor", "não completou o tratamento" ou "falhou". Os cães foram excluídos do estudo se tivessem sido tratados em outro serviço, não tivessem sido tratados para SA, ou se fossem identificados abscessos, massas ou fístulas nos sacos anais. Resultados - Dezenove cães eram machos e 14 fêmeas. Vinte e quatro raças foram incluídas. A idade média no surgimento da doença foi de 4,4 anos. O ECC médio foi 5,8 em 9. A qualidade das fezes foi ruim em sete de 33 cães e normal em 22 de 33 casos. A dermatite atópica foi a comorbidade mais comum (12 de 33). O tratamento tipicamente consistiu de lavagem dos sacos anais com solução salina seguido de infusão de uma solução comercial contendo esteroide/antibiótico/antifúngico. O tratamento foi repetido em média 2,9 vezes. Resolução da SA foi alcançada em 24 de 33 casos, os sinais clínicos se resolveram de acordo com o tutor em quatro de 33 casos, cinco de 33 casos não completaram o tratamento e em nenhum caso houve falha terapêutica. Conclusões e relevância clínica - Tratamento tópico com lavagem e infusão é eficaz para tratar SA em cães.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Hostage to history - questioning the duration of systemic antimicrobial therapy for the treatment of canine superficial bacterial folliculitis.

Current guidelines for the use of systemic antimicrobials for the treatment of superficial bacterial folliculitis in dogs include the recommendation that the disease be treated for a minimum of 3 weeks and for at least 1 week beyond clinical resolution. With increasing antimicrobial resistance being noted for bacteria involved in this condition, as well as the increased use of evidence-based medicine, this dogma needs to be reevaluated.

Validation of the 0-10 verbal numeric scale for assessment of pruritus severity in dogs.

BACKGROUND: The pruritus Visual Analog Scale (pVAS) is currently the only validated tool for assessing canine pruritus. A verbal numeric scale (VNS) offers an alternative if clients are not present or able to complete the pVAS. HYPOTHESIS/OBJECTIVE: To validate the 0-10 VNS and evaluate its interchangeability with the pVAS. ANIMALS: 251 dogs were included in the study. MATERIALS AND METHODS: Dog owners were asked to assess their pet's pruritus level using the pVAS, the 0-10 VNS and the verbal rating categories (mild, moderate, severe) in one or two subsequent visits. To be valid, VNS must satisfy the following: correlate with pVAS (criterion validity); indicate reduction in itch score after an antipruritic intervention (construct validity); and have scores related to the verbal rating categories that are significantly different (content validity). VNS and pVAS interchangeability and the percentage of clients that preferred the VNS and pVAS also were evaluated. RESULTS: The VNS and pVAS correlation for visits 1 and 2 was good (rICC = 0.9) and excellent (rICC = 0.94). The VNS scores were significantly decreased after antipruritic interventions (P < 0.001). The VNS scores associated with the verbal rating scale categories (mild, moderate and severe) were significantly different (P < 0.001). The 95% limits of agreement for the pVAS and VAS were outside the limit of acceptability of ±2 (-2.0, 2.57). Most clients (69%) preferred the pVAS to the VNS. CONCLUSIONS AND CLINICAL RELEVANCE: The VNS is a valid scale to evaluate canine pruritus; however, the VNS and pVAS are not interchangeable.

Assembly of infectious Kaposi's sarcoma-associated herpesvirus progeny requires formation of a pORF19 pentamer.

Herpesviruses cause severe diseases particularly in immunocompromised patients. Both genome packaging and release from the capsid require a unique portal channel occupying one of the 12 capsid vertices. Here, we report the 2.6 Å crystal structure of the pentameric pORF19 of the γ-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) resembling the portal cap that seals this portal channel. We also present the structure of its ß-herpesviral ortholog, revealing a striking structural similarity to its α- and γ-herpesviral counterparts despite apparent differences in capsid association. We demonstrate pORF19 pentamer formation in solution and provide insights into how pentamerization is triggered in infected cells. Mutagenesis in its lateral interfaces blocked pORF19 pentamerization and severely affected KSHV capsid assembly and production of infectious progeny. Our results pave the way to better understand the role of pORF19 in capsid assembly and identify a potential novel drug target for the treatment of herpesvirus-induced diseases.

Cost evaluation of PAGE-B risk score guided HCC surveillance in patients with treated chronic hepatitis B.

BACKGROUND: The PAGE-B score (Platelet Age GEnder-HBV) selects chronic hepatitis B (cHB) patients showing no relevant 5-year risk for hepatocellular carcinoma (HCC). We, therefore, explored potential cost reduction following the introduction of a PAGE-B tailored ultrasound screening in a single center cohort of cHB patients receiving stable antiviral therapy. METHODS: cHB patients attending throughout the year 2018 were documented. Patients eligible for PAGE-B score were classified into high (≥18 points), intermediate (10-17 points) and low (≤9 points) HCC risk groups. Patients of the low HCC risk group could postpone HCC screening to reduce HCC screening expenses. Full costs for hepatic ultrasound were assessed. RESULTS: Throughout the year cHB patients (n = 607) attended our clinic, which included PAGE-B eligible patients (n = 227, 37.4%) of whom n = 94 (15.8%) were allocated to the low HCC risk group. Sonographic HCC screening during a median exam time of 12.4 min (IQR 9.2-17.2) resulted in total costs of 22.82 Euro/exam. Additional opportunistic expenses caused by patient's lost earnings or productivity were 15.6-17.5 €/exam and 26.7 €/exam, respectively. Following a PAGE-B tailored HCC screening at our institution annual full costs for cHB patients could be reduced by 15.51%, which equals a cost reduction by 1.91% for our total sonography unit. In comparison, 1.35% up to 7.65% of HBV-infected patients of Caucasian descent could postpone HCC screening according to population-based estimates from Germany. CONCLUSIONS: PAGE-B risk score adapted screening for HCC is an efficient and cost neutral tool to reduce costs for sonography in Caucasian patients with chronic hepatitis B receiving antiviral treatment.

High pretreatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein (AFP) is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static AFP values is limited and the clinical potential is a matter of ongoing scientific discussion. OBJECTIVE: We here evaluated the prognostic impact of pretreatment static and dynamic AFP variables on overall survival of hepatocellular carcinoma patients in a Western cohort. METHODS: Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg University Mainz between 1998 and 2014 and two available pretreatment AFP-values (AFP-slope) were retrospectively analysed. Clinicopathological baseline parameters, pretreatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan-Meier analyses and Cox regression models. RESULTS: High static and dynamic AFP variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child-Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic AFP variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static AFP values. CONCLUSION: Static and dynamic AFP variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.

Structural aspects of the aging invertebrate brain.

Aging is characterized by a decline in neuronal function in all animal species investigated so far. Functional changes are accompanied by and may be in part caused by, structurally visible degenerative changes in neurons. In the mammalian brain, normal aging shows abnormalities in dendrites and axons, as well as ultrastructural changes in synapses, rather than global neuron loss. The analysis of the structural features of aging neurons, as well as their causal link to molecular mechanisms on the one hand, and the functional decline on the other hand is crucial in order to understand the aging process in the brain. Invertebrate model organisms like Drosophila and C. elegans offer the opportunity to apply a forward genetic approach to the analysis of aging. In the present review, we aim to summarize findings concerning abnormalities in morphology and ultrastructure in invertebrate brains during normal aging and compare them to what is known for the mammalian brain. It becomes clear that despite of their considerably shorter life span, invertebrates display several age-related changes very similar to the mammalian condition, including the retraction of dendritic and axonal branches at specific locations, changes in synaptic density and increased accumulation of presynaptic protein complexes. We anticipate that continued research efforts in invertebrate systems will significantly contribute to reveal (and possibly manipulate) the molecular/cellular pathways leading to neuronal aging in the mammalian brain.

Microscopical discrimination of human head hairs sharing a mitochondrial haplogroup.

In forensic analyses, determining the level of consensus among examiners for hair comparison conclusions and ancestry identifications is important for assessing the scientific validity of microscopical hair examinations. Here, we present data from an interlaboratory study on the accuracy of microscopical hair comparisons among a subset of experienced hair examiners currently analyzing hair in forensic laboratories across the United States. We examined how well microscopical analysis of hair can reliably be used to differentiate hair samples, many of which were macroscopically similar. Using cut hair samples, many sharing similar macroscopic and microscopic features, collected from individuals who share the same mitochondrial haplogroup as an indication of genetic relatedness, we tested multiple aspects that could impact hair comparisons. This research tested the extent to which morphological features related to ancestry and hair length influence conclusions. Microscopical hair examinations yielded accurate assessments of inclusion/exclusion relative to the reference samples among 85% of the pairwise comparisons. We found shorter hairs had reduced levels of accuracy and hairs from populations examiners were not familiar with may have impacted their ability to resolve features. The reliability of ancestry determinations is not yet clear, but we found indications that the existing categories are only somewhat related to current ethnic and genetic variation. Our results provide support for the continued utility of microscopical comparison of hairs within forensic laboratories and to advocate for a combined analytical approach using both microscopical analysis and mtDNA data on all forensic analyses of hair.

High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion. OBJECTIVE: We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort. METHODS: Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan-Meier analyses and Cox regression models. RESULTS: High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child-Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values. CONCLUSION: Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.

Validation of prognostic accuracy of MESH, HKLC, and BCLC classifications in a large German cohort of hepatocellular carcinoma patients.

BACKGROUND AND AIM: The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly used to classify hepatocellular carcinoma (HCC) patients. However, other staging classification schemes have been proposed. We aimed to compare the prognostic accuracy of the Hong Kong Liver Cancer Staging (HKLC), the Model to Estimate Survival for HCC (MESH), and the BCLC staging systems using a Western cohort of HCC patients. METHODS: We retrospectively analyzed 918 patients diagnosed with HCC treated at the University Medical Center of Mainz between 2005 and 2014. We compared the predictive power of survival time of the BCLC, HKLC, and MESH. Predictive ability was tested using the integrated Brier score (IBS) and Harrell's C index. RESULTS: Kaplan-Meier analyses showed significant differences in survival between stages defined by the BCLC, HKLC, and MESH. The HKLC classification demonstrated a more robust classification concordance and lower prediction error compared to the BCLC and MESH. In addition, we found that the BCLC offers superior predictive ability to the MESH in the first four years, whereas the MESH is superior for long-term predictions. CONCLUSION: Our analyses confirm the prognostic value of three different HCC scoring systems. When compared, the HKLC provides superior prognostication ability.

Patulous Eustachian tube and palatine defect in a Dachshund with chronic unilateral otitis externa and otitis media.

BACKGROUND: Patulous Eustachian tube (pET) is a rare dysfunction of the Eustachian tube described in humans. It is characterized by failure of the ET to close, resulting in unrestricted passage of air, sound and material between the nasopharynx and the middle ear. OBJECTIVE: To report a case of pET associated with otitis in a dog. ANIMAL: A 6-year old-female spayed Dachshund dog. METHODS AND MATERIALS: Otoscopic examination, cytological evaluation, culture and susceptibility, computerized tomography (CT), video-otoscopic flushing and surgery. RESULTS: Left ear otoscopic examination revealed erythema, purulent frothy discharge, ceruminous gland hyperplasia, stenosis and a partial tear of the tympanum. Cytological evaluation from the left external canal showed neutrophils, macrophages, rods and cocci. Aerobic culture showed predominantly multidrug-resistant Pseudomonas aeruginosa. The CT findings of the left ear included chronic changes in the external canal, marked lysis of the tympanic bulla and marked dilation of the ET. During video-otoscope flushing, saline drained through the mouth. Bilateral incomplete hypoplasia of the soft palate was noted. Total ear canal ablation and bulla osteotomy with ET dissection were curative. Histopathological findings were compatible with chronic otitis externa (OE) and media. CONCLUSION AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first case of pET described in animals. The ET dysfunction and palatine defect were likely the cause of the otitis in this dog. Clinicians should investigate pET in animals with signs of OE characterized by frothy liquid and food fragments in the ear canal in addition to sneezing after drinking water.

The biology of human hair: A multidisciplinary review.

In the last century, human scalp hair morphology has been studied from multiple, and sometimes mutually exclusive, perspectives by anthropologists, biologists, geneticists, forensic scientists, and cosmetic scientists. Here, we review and synthesize historical and current research on hair to better understand the scientific basis and biological implications of hair microstructure and morphology. We revisit the origins of existing nomenclature regarding hair morphology and classifications, discuss the currently recognized limitations to hair analysis within the varied scientific disciplines studying hair, point out aspects of hair biology that remain unknown, and the great potential for integrating these diverse perspectives and expertise in future scientific investigations, while highlighting the benefits of combining nondestructive microscopical analysis with chemical and genomic analyses for explicating hair biology. Further, we propose consensus terminology for root growth stages through descriptions and images that will aid in the morphological and microscopical analysis of human scalp hair, thereby reducing confusion and the promulgation of inaccurate information that is presently in the literature.

Sarcopenia as prognostic factor for survival after orthotopic liver transplantation.

BACKGROUND AND AIM: Body composition has emerged as a prognostic factor for end-stage liver disease. We therefore investigated muscle mass, body fat and other clinical-pathological variables as predictors of posttransplant survival. METHODS: A total of 368 patients, who underwent orthotopic liver transplantation (OLT) at our institution, were assessed prior to OLT and followed for a median of 9.0 years (range 2.0-10.0 years) after OLT. Psoas, erector spinae and the combined paraspinal muscle area, as well as the corresponding indices normalized by body-height squared, were quantified by a lumbar (L3) cross-sectional computed tomography. In addition, absolute body fat and bone density were estimated by the same computed tomography approach. RESULTS: Paraspinal muscle index (PSMI) (hazard ratio 0.955, P = 0.039) and hepatitis C (hazard rati 1.498, P = 0.038) were independently associated with post-OLT mortality. In contrast, body fat and bone density did not significantly affect post-OLT outcome (P > 0.05). The PSMI also predicted one-year posttransplant mortality with a receiver operating characteristics-area under the curve of 0.671 [95% confidence interval (CI) 0.589-0.753, P < 0.001) in male patients and outperformed individual psoas and erector spinae muscle group assessments in this regard. In male patients, a defined PSMI cutoff (<18.41 cm/m) was identified as suitable determinant for sarcopenia and posttransplant one-year mortality. In female OLT-recipients, however, sarcopenia was not predictive for patient survival und a women-specific cutoff could not be derived from this study. CONCLUSIONS: Taken together this analysis provides evidence, which PSMI is a relevant marker for muscle mass and that sarcopenia is an independent predictor of early post-OLT survival in male patients.

Targeting Kaposi's Sarcoma-Associated Herpesvirus ORF21 Tyrosine Kinase and Viral Lytic Reactivation by Tyrosine Kinase Inhibitors Approved for Clinical Use.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of three human malignancies: Kaposi's sarcoma, primary effusion lymphoma, and the plasma cell variant of multicentric Castleman disease. Previous research has shown that several cellular tyrosine kinases play crucial roles during several steps in the virus replication cycle. Two KSHV proteins also have protein kinase function: open reading frame (ORF) 36 encodes a serine-threonine kinase, while ORF21 encodes a thymidine kinase (TK), which has recently been found to be an efficient tyrosine kinase. In this study, we explore the role of the ORF21 tyrosine kinase function in KSHV lytic replication. By generating a recombinant KSHV mutant with an enzymatically inactive ORF21 protein, we show that the tyrosine kinase function of ORF21/TK is not required for the progression of the lytic replication in tissue culture but that it is essential for the phosphorylation and activation to toxic moieties of the antiviral drugs zidovudine and brivudine. In addition, we identify several tyrosine kinase inhibitors, already in clinical use against human malignancies, which potently inhibit not only ORF21 TK kinase function but also viral lytic reactivation and the development of KSHV-infected endothelial tumors in mice. Since they target both cellular tyrosine kinases and a viral kinase, some of these compounds might find a use in the treatment of KSHV-associated malignancies.IMPORTANCE Our findings address the role of KSHV ORF21 as a tyrosine kinase during lytic replication and the activation of prodrugs in KSHV-infected cells. We also show the potential of selected clinically approved tyrosine kinase inhibitors to inhibit KSHV TK, KSHV lytic replication, infectious virion release, and the development of an endothelial tumor. Since they target both cellular tyrosine kinases supporting productive viral replication and a viral kinase, these drugs, which are already approved for clinical use, may be suitable for repurposing for the treatment of KSHV-related tumors in AIDS patients or transplant recipients.