265 research outputs found
Immortalized human keratinocytes: A model system to study the efficacy of therapeutic drugs in response to the chemical warfare agent sulfur mustard (HD)
Cytokines have been established as biomarkers to detect exposure of
cells to chemical warfare agents such as sulfur mustard
(2,2'-dichlorodiethyl sulfide, HD). In this study cultured normal and
SV40 immortalized human epidermal keratinocyte (NHEK/IHEK) cells were
compared as potential model systems to measure the efficacy of
therapeutic drugs against HD. Immortalized human epidermal
keratinocytes resemble their primary cell counterparts but have the
advantage of being carried through long-term culture. Immortalized
cells also provide consistency and durability and are less costly than
primary keratinocytes. Immunoassay studies were performed to examine
the response of these two cell lines to HD. We found that both normal
and immortalized NHEKs secreted the pro-inflammatory mediator
interleukin-8 (IL-8) when exposed to HD. However, a major difference
was observed between the NHEK cell line 6207 and IHEK cell line 425.
IHEK cell line 425 produced higher levels of Interleuken-8 then those
of its normal counterpart cell line 6207. This observation is
significant since therapeutic drugs such as ibuprofen, which depress
cytokine production, may not allow these biomarkers to be detected
efficiently in experimental analysis of certain NHEK cell lines. The
fact that Il-8 production higher in cell line 425 cell makes this in
vitro model a potential screening tool to study the efficacy of drugs
that suppress production of cytokine markers
Culture Conversion Among HIV Co-Infected Multidrug-Resistant Tuberculosis Patients in Tugela Ferry, South Africa
Little is known about the time to sputum culture conversion in MDR-TB patients co-infected with HIV, although such patients have, historically, had poor outcomes. We describe culture conversion rates among MDR-TB patients with and without HIV-co-infection in a TB-endemic, high-HIV prevalent, resource-limited setting.Patients with culture-proven MDR-TB were treated with a standardized second-line regimen. Sputum cultures were taken monthly and conversion was defined as two negative cultures taken at least one month apart. Time-to-conversion was measured from the day of initiation of MDR-TB therapy. Subjects with HIV received antiretroviral therapy (ART) regardless of CD4 count.Among 45 MDR-TB patients, 36 (80%) were HIV-co-infected. Overall, 40 (89%) of the 45 patients culture-converted within the first six months and there was no difference in the proportion who converted based on HIV status. Median time-to-conversion was 62 days (IQR 48-111). Among the five patients who did not culture convert, three died, one was transferred to another facility, and one refused further treatment before completing 6 months of therapy. Thus, no patients remained persistently culture-positive at 6 months of therapy.With concurrent second-line TB and ART medications, MDR-TB/HIV co-infected patients can achieve culture conversion rates and times similar to those reported from HIV-negative patients worldwide. Future studies are needed to examine whether similar cure rates are achieved at the end of MDR-TB treatment and to determine the optimal use and timing of ART in the setting of MDR-TB treatment
Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: a review
Neonatal encephalopathy (NE) following perinatal asphyxia (PA) is considered an important cause of later neurodevelopmental impairment in infants born at term. This review discusses long-term consequences for general cognitive functioning, educational achievement, neuropsychological functioning and behavior. In all areas reviewed, the outcome of children with mild NE is consistently positive and the outcome of children with severe NE consistently negative. However, children with moderate NE form a more heterogeneous group with respect to outcome. On average, intelligence scores are below those of children with mild NE and age-matched peers, but within the normal range. With respect to educational achievement, difficulties have been found in the domains reading, spelling and arithmetic/mathematics. So far, studies of neuropsychological functioning have yielded ambiguous results in children with moderate NE. A few studies suggest elevated rates of hyperactivity in children with moderate NE and autism in children with moderate and severe NE. Conclusion: Behavioral monitoring is required for all children with NE. In addition, systematic, detailed neuropsychological examination is needed especially for children with moderate NE
Behavioral Profiles of Affected and Unaffected Siblings of Children with Autism: Contribution of Measures of Mother–Infant Interaction and Nonverbal Communication
We investigated whether deficits in social gaze and affect and in joint attention behaviors are evident within the first year of life among siblings of children with autism who go on to be diagnosed with autism or ASD (ASD) and siblings who are non-diagnosed (NoASD-sib) compared to low-risk controls. The ASD group did not differ from the other two groups at 6 months of age in the frequency of gaze, smiles, and vocalizations directed toward the caregiver, nor in their sensitivity to her withdrawal from interaction. However, by 12 months, infants in the ASD group exhibited lower rates of joint attention and requesting behaviors. In contrast, NoASD-sibs did not differ from comparison infants on any variables of interest at 6 and 12 months
Bayesian Modeling of the Yeast SH3 Domain Interactome Predicts Spatiotemporal Dynamics of Endocytosis Proteins
A genome-scale specificity and interaction map for yeast SH3 domain-containing proteins reveal how family members show selective binding to target proteins and predicts the dynamic localization of new candidate endocytosis proteins
Cavity-enhanced direct frequency comb spectroscopy
Cavity-enhanced direct frequency comb spectroscopy combines broad spectral
bandwidth, high spectral resolution, precise frequency calibration, and
ultrahigh detection sensitivity, all in one experimental platform based on an
optical frequency comb interacting with a high-finesse optical cavity. Precise
control of the optical frequency comb allows highly efficient, coherent
coupling of individual comb components with corresponding resonant modes of the
high-finesse cavity. The long cavity lifetime dramatically enhances the
effective interaction between the light field and intracavity matter,
increasing the sensitivity for measurement of optical losses by a factor that
is on the order of the cavity finesse. The use of low-dispersion mirrors
permits almost the entire spectral bandwidth of the frequency comb to be
employed for detection, covering a range of ~10% of the actual optical
frequency. The light transmitted from the cavity is spectrally resolved to
provide a multitude of detection channels with spectral resolutions ranging
from a several gigahertz to hundreds of kilohertz. In this review we will
discuss the principle of cavity-enhanced direct frequency comb spectroscopy and
the various implementations of such systems. In particular, we discuss several
types of UV, optical, and IR frequency comb sources and optical cavity designs
that can be used for specific spectroscopic applications. We present several
cavity-comb coupling methods to take advantage of the broad spectral bandwidth
and narrow spectral components of a frequency comb. Finally, we present a
series of experimental measurements on trace gas detections, human breath
analysis, and characterization of cold molecular beams.Comment: 36 pages, 27 figure
Correction. "The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms" Leukemia. 2022 Jul;36(7):1720-1748
We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms
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