Update from the 5th Edition of the WHO Classification of Nasal, Paranasal, and Skull Base Tumors: Imaging Overview with Histopathologic and Genetic Correlation.

Sinonasal and skull base tumors are a heterogeneous group of neoplasms with considerable histologic variation and overlapping imaging features. In 2022, the World Health Organization updated the head and neck tumor classification, further emphasizing the importance of molecular data and genetic alterations in sinonasal neoplasms. The changes include the addition of new entities and discussion of emerging entities, as well as changes to the taxonomy and characterization of tumors. The new classification focuses on entities that develop in these sites either exclusively (eg, olfactory neuroblastoma) or most frequently. Another change includes reduction in the number of categories by creating separate category-specific chapters for soft-tissue, hematolymphoid, and neuroectodermal lesions. In this review, we briefly discuss the various categories in the new classification with a more detailed description of the 2 new entities (SWItch/Sucrose Non-Fermentable complex-deficient sinonasal carcinomas and human papillomavirus-related multiphenotypic sinonasal carcinoma). We also highlight the emerging entities including IDH-mutant sinonasal malignancies and DEK-AFF2 carcinoma, presently classified as sinonasal undifferentiated carcinoma and nonkeratinizing squamous cell carcinoma, respectively.

Combined Diffusion Tensor Imaging and Apparent Transverse Relaxation Rate Differentiate Parkinson Disease and Atypical Parkinsonism.

BACKGROUND AND PURPOSE: Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. MATERIALS AND METHODS: A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. RESULTS: Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson disease; those with Parkinson disease from those with multiple system atrophy/progressive supranuclear palsy; and those with Parkinson disease from those with multiple system atrophy; but not those with Parkinson disease from those with progressive supranuclear palsy, or those with multiple system atrophy from those with progressive supranuclear palsy. CONCLUSIONS: DTI and the apparent transverse relaxation rate provide different but complementary information for different parkinsonisms. Combined DTI and apparent transverse relaxation rate may be a superior marker for the differential diagnosis of parkinsonisms.

Animal models to improve our understanding and treatment of suicidal behavior.

Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes. Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide. In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic-pituitary-adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals. We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models. Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies. Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio.

Enlarged vestibular aqueducts and other inner-ear abnormalities in patients with Down syndrome.

BACKGROUND: Histopathological anomalies of inner-ear structures in individuals with Down syndrome have been well documented; however, few studies have examined the radiological features. METHODS: A retrospective study was conducted of temporal bone computed tomography images in 38 individuals (75 ears) with Down syndrome to evaluate the prevalence of inner-ear abnormalities and assess vestibular aqueduct widths. RESULTS: Inner-ear anomalies were identified in 20 of the 38 individuals (52.6 per cent). Seven of the 75 temporal bones (9.3 per cent) were found to have higher than previously reported. A dilated internal auditory canal and vestibule were more common among the present study group, while prior studies have demonstrated internal auditory canal stenosis and decreased vestibule size. CONCLUSION: Down syndrome patients exhibit a high prevalence of dysplastic inner-ear features that confer substantial risk of sensorineural hearing loss. Computed tomography is a useful screening aid to detect inner-ear abnormalities, particularly enlarged vestibular aqueducts, which cause preventable sensorineural hearing loss in this population.

Exploration of a haloarchaeon, Halostagnicola larsenii, isolated from rock pit sea water, West Coast of Maharashtra, India, for the production of bacteriorhodopsin.

AIMS: The aim of the present investigation was to isolate haloarchaea from rock pit sea water, West Coast of India and to explore their potential in the production of bacteriorhodopsin (BR) which converts light energy into electrical energy. METHODS AND RESULTS: Haloarchaeal strains were isolated from rock pit sea water samples collected from Rock garden, Malvan, West Coast of India. Based on morphological, physiological and biochemical characteristics, and 16S rRNA gene sequencing, all the 11 strains were identified as Halostagnicola larsenii. All the strains require at least 1·5 mol l(-1) NaCl for growth; grow optimally in the range of 3·5-5·2 mol l(-1) NaCl. BR was detected in all the strains ranging from 0·035 to 0·258 g l(-1) . All 11 strains showed conversion of light energy into electrical energy in the range of 0·7-44·2 mV, when exposed to sunlight. CONCLUSIONS: A haloarchaeon, Hst. larsenii is isolated from rock pit sea water and demonstrated to have BR that converted light energy into electrical energy. SIGNIFICANCE AND IMPACT OF THE STUDY: The present investigation is presumably the first report of the isolation of Hst. larsenii from low salinity environment and its potential in production of BR. The haloarchaeon could be explored for the generation of electrical energy.

Bioremediation of nitroexplosive wastewater by an yeast isolate Pichia sydowiorum MCM Y-3 in fixed film bioreactor.

Nitroexplosives are essential for security and defense of the nation and hence their production continues. Their residues and transformed products, released in the environment are toxic to both terrestrial and aquatic life. This necessitates remediation of wastewaters containing such hazardous chemicals to reduce threat to human health and environment. Bioremediation technologies using microorganisms become the present day choice. High Melting Explosive (HMX) is one of the nitroexplosives produced by nitration of hexamine using ammonium nitrate and acetic anhydride and hence the wastewater bears high concentration of nitrate and acetate. The present investigation describes potential of a soil isolate of yeast Pichia sydowiorum MCM Y-3, for remediation of HMX wastewater in fixed film bioreactor (FFBR). The flask culture studies showed appreciable growth of the organism in HMX wastewater under shake culture condition within 5-6 days of incubation at ambient temperature (28 +/- 2 degrees C). The FFBR process operated in both batch and continuous mode, with Hydraulic Retention Time (HRT) of 1 week resulted in 50-55% removal in nitrate, 70-88% in acetate, 50-66% in COD, and 28-50% in HMX content. Continuous operation of the reactor showed better removal of nitrate as compared to that in the batch operation, while removal of acetate and COD was comparable in both the modes of operation of the reactor. Insertion of baffles in the reactor increased efficiency of the reactor. Thus, FFBR developed with baffles and operated in continuous mode will be beneficial for bioremediation of high nitrate and acetate containing wastewater using the culture of P. sydowiorum.

A prospective cohort of American Indian and Alaska Native people: study design, methods, and implementation.

In 2001, the National Cancer Institute funded three centers to test the feasibility of establishing a cohort of American Indian and Alaska Native people. Participating tribal organizations named the study EARTH (Education and Research Towards Health). This paper describes the study methods. A computerized data collection and tracking system was developed using audio computer-assisted survey methodology with touch screens. Data were collected on diet, physical activity, lifestyle and cultural practices, medical and reproductive history, and family history of heart disease, diabetes, and cancer. In addition, a small panel of medical measurements was obtained, including height, weight, waist and hip circumferences, blood pressure, and a lipid panel plus glucose. At the completion of the enrollment visit, data were used to provide immediate health feedback to study participants. During the initial funding period, the authors anticipate enrolling 16,000 American Indian and Alaska Native participants. The age distribution of the study population was similar to that reported in the 2000 US Census for the relevant populations. A component critical to the success of the EARTH Study has been the partnerships with tribal members. The study has focused on involvement of American Indian and Alaska Native communities in development and implementation and on provision of feedback to participants and communities.

Atlantoaxial dislocation in idiopathic cervical dystonia.

We report a case of severe cervical spondylosis and atlantoaxial dislocation (AAD) in association with idiopathic cervical dystonia (ICD) in a middle-aged male. To our knowledge, this is the first case of ICD reported in association with AAD.

The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene.

The eyeless inbred mouse strain ZRDCT has long served as a spontaneous model for human anophthalmia and the evolutionary reduction of eyes that has occurred in some naturally blind mammals. ZRDCT mice have orbits but lack eyes and optic tracts and have hypothalamic abnormalities. Segregation data suggest that a small number of interacting genes are responsible, including at least one major recessive locus, ey1. Although predicted since the 1940s, these loci were never identified. We mapped ey1 to chromosome 18 using an F2 genome scan and there found a Met10-->Leu mutation in Rx/rax, a homeobox gene that is expressed in the anterior headfold, developing retina, pineal, and hypothalamus and is translated via a leaky scanning mechanism. The mutation affects a conserved AUG codon that functions as an alternative translation initiation site and consequently reduces the abundance of Rx protein. In contrast to a targeted Rx null allele, which causes anophthalmia, central nervous system defects, and neonatal death, the hypomorphic M10L allele is fully viable.

Helping norms in relation to religious affiliation.

The authors used vignettes to solicit each participant's estimate of the likelihood of help and his/her recommendation for or against helping a student who needed to borrow another student's class notes. The study had a 2 (Hindu vs. Muslim participant) x 2 (participant's gender) x 2 (liking vs. disliking relationship) x 2 (justified vs. unjustified need for help) x 2 (low vs. high cost of helping) factorial design with 15 participants per cell. Estimated likelihood of help was higher among the female than among the male participants, with the liking than with the disliking relationship, and with the low rather than with the high cost of helping. The Hindu participants gave lower estimates of the likelihood of help than did the Muslim participants with the disliking relationship and with the unjustified need for help. Intracommunal helping, irrespective of contextual variations, may have been a stronger social norm for the Muslim than for the Hindu participants, probably because of the former's minority status in India and, more important, the Islamic prescription of communal brotherhood. Even though both communities are deemed collectivist, the Indian Muslim participants' helping norms appeared to be more obligation oriented and less option oriented than those of the Indian Hindu participants.

Fin-de-siècle ranking of important psychologists by a sample of undergraduate students enrolled in history of psychology.

134 undergraduate students of the history of psychology from 1998 through 2000 were requested to name three psychologists in order of importance, eminence, or influence within as well as outside the discipline of psychology. Salient was confirmation of Sigmund Freud as outranking other psychologists by a wide margin.

Modulation of heart fibroblast migration and collagen gel contraction by IGF-I.

Dynamic interactions between cells and the extracellular matrix are essential in the regulation of a number of cellular processes including migration, adhesion, proliferation and differentiation. A variety of factors have been identified which modulate these interactions including transforming growth factor-beta, platelet-derived growth factor and others. Insulin-like growth factors have been shown to regulate collagen production by heart fibroblasts; however, the effects of this growth factor on the interactions of heart fibroblasts with the extracellular matrix have not been examined. The present studies were carried out to determine the effects of IGF-I on the ability of fibroblasts to interact with the extracellular matrix and to begin to determine the mechanisms of this response. These experiments illustrate that IGF-I treatment results in increased migration, collagen reorganization and gel contraction by heart fibroblasts. IGF-I has been shown to activate both the mitogen-activated protein kinase and phophatidylinositol-3 kinase pathways in isolated cells. Experiments with pharmacological antagonists of these pathways indicate that the mitogen-activated protein kinase pathway is essential for IGF-I stimulated collagen gel contraction by fibroblasts. These studies illustrate that IGF-I modulates the ability of fibroblasts to interact with the collagen matrix and that activation of multiple signaling pathways by IGF-I may produce distinct downstream responses in these cells.

Ankylosing spondylitis presenting with discitis.

Ankylosing spondylitis is not an uncommon disease worldwide, yet is relatively rare in Bahrain. There is a typical pattern of joint involvement in cases of ankylosing spondylitis, but the presentation of discitis is rare. We present a case of a patient presenting with backache and was diagnosed to have discitis. The diagnosis of ankylosing spondylitis was made only after he was found to be Human Leukocyte Antigen-B27 positive. This is the first case report of ankylosing spondylitis presenting as discitis in Bahrain.

Ankylosing spondylitis presenting with discitis.

Ankylosing spondylitis is not an uncommon disease worldwide, yet is relatively rare in Bahrain. There is a typical pattern of joint involvement in cases of ankylosing spondylitis, but the presentation of discitis is rare. We present a case of a patient presenting with backache and was diagnosed to have discitis. The diagnosis of ankylosing spondylitis was made only after he was found to be Human Leukocyte Antigen-827 positive. This is the first case report of ankylosing spondylitis presenting as discitis in Bahrain.

Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis.

We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 and is largely restricted to the developing eye. Math5 retinal expression precedes differentiation of the first neurons and persists within progenitor cells until after birth. To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos. Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey eye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-dependent manner. These results link Pax6 to the process of retinal neurogenesis and provide the first molecular correlate for the dosage-sensitivity of the Pax6 phenotype. During retinogenesis, Math5 is expressed significantly before NeuroD, Ngn2 or Mash1. To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection of either mouse gene into the frog retina caused an increase in differentiated bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus blastomeres produced an expanded retinal phenotype. We propose that Math5 acts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.

Wegener's granulomatosis. First case report in Bahrain.

Formerly a fatal condition, Wegener's granulomatosis is now treated with good results. Although the annual incidence of Wegener's granulomatosis in the general population is not known, most European and American studies revealed an incidence in the range of one for every 250,000 of the population. The estimated total population of Bahrain as of June 1997 is 586,110; here we report the first diagnosed case of Wegener's granulomatosis in Bahrain. Our patient presented with epistaxis, and from the clinical features, the very high ESR, the operative, histopathological and the radiological findings, and a high index of suspicion we could confirm the diagnosis along with the appropriate immunological test (positive cANCA). Standard treatment with cytotoxic agents and corticosteroids has been used. On follow-up the patient has shown a progressive improvement in her clinical and laboratory parameters.

The genetic sequence of retinal development in the ciliary margin of the Xenopus eye.

The ciliary marginal zone is a perpetually self-renewing proliferative neuroepithelium at the perimeter of the retina in amphibians and fish. In the ciliary marginal zone (CMZ), cells are spatially ordered with respect to cellular development, deep stem cells being most peripheral and differentiating retinal progenitors being most central. This spatial gradient in the CMZ recapitulates embryonic retinogenesis and provides a powerful system to examine the relative order of gene expression during this process. A number of neurogenic and proneural genes have been described to have interacting roles in the development of the vertebrate nervous system, and so it is of major importance to put these genes in a hierarchical pathway. In no other system yet described are the developmental stages of neurogenesis arrayed so clearly in a spatial pattern as in the CMZ. We have therefore taken advantage of this system, using double in situ hybridizations on cross sections of the CMZ, to compare the spatial patterns of 15 proneural, neurogenic, and other genes involved in early and late phases of retinal development. In addition, we have positioned these expression patterns with respect to cell division. What emerges from this work is a spatial ordering of gene expression that predicts a genetic hierarchy governing vertebrate retinogenesis. By injecting messenger RNA for some of these genes into blastomeres of the Xenopus embryo and examining the effects on expression of the putative downstream genes, we have been able to corroborate some of the relationships between genes predicted to act sequentially.

Attribution as a function of agential distance in a causal chain.

The hypothesis that causality and blame will be differently affected by agential distance within a two-step causal chain was tested. A hypothetical medical accident was presented to 360 female college students in India, who gave causality, blame, or punishment judgments about either the proximal agent or the distal agent. The study had a 2 (proximal vs. distal agent) x 2 (high vs. low extenuation) x 2 (mild vs. severe outcome) x 3 (casuality, blame, or punishment judgments) fully crossed, between-subjects factorial design, with 15 participants per cell. In support of the basic hypothesis, more blame and punishment were assigned to the distal agent than to the proximal agent, whereas agential distance did not affect causal attribution. Extenuation was effective on causality and blame judgments only when the outcome was mild, and there was no effect of extenuation on punishment judgments, irrespective of outcome severity.

Cardiac fibroblasts form and function.

The formation and structure of the extracellular matrix (ECM) that makes up the cardiac interstitum is well known yet the underlying mechanisms that regulate the interstitum are poorly known. This review focuses on the role of the cardiac fibroblast in the formation and regulation of the ECM components during cardiac development and in response to physiological and pathological stimulation. The role of ECM receptors (integrins), cellular phenotype, and chemical and mechanical signaling by cardiac fibroblasts are discussed.