Isolated and solvated chiroptical behavior in conformationally flexible butanamines.

The nonresonant optical activity of two highly flexible aliphatic amines, (2R)-3-methyl-2-butanamine (R-MBA) and (2R)-(3,3)-dimethyl-2-butanamine (R-DMBA), has been probed under isolated and solvated conditions to examine the roles of conformational isomerism and to explore the influence of extrinsic perturbations. The optical rotatory dispersion (ORD) measured in six solvents presented uniformly negative rotatory powers over the 320-590 nm region, with the long-wavelength magnitude of chiroptical response growing nearly monotonically as the dielectric constant of the surroundings diminished. The intrinsic specific optical rotation, α λ T (in deg dm-1 [g/mL]-1 ), extracted for ambient vapor-phase samples of R-MBA [-11.031(98) and -2.29 (11)] and R-DMBA [-9.434 (72) and -1.350 (48)] at 355 and 633 nm were best reproduced by counterintuitive solvents of high polarity (yet low polarizability) like acetonitrile and methanol. Attempts to interpret observed spectral signatures quantitatively relied on the linear-response frameworks of density-functional theory (B3LYP, cam-B3LYP, and dispersion-corrected analogs) and coupled-cluster theory (CCSD), with variants of the polarizable continuum model (PCM) deployed to account for the effects of implicit solvation. Building on the identification of several low-lying equilibrium geometries (nine for R-MBA and three for R-DMBA), ensemble-averaged ORD profiles were calculated at T = 300 K by means of the independent-conformer ansatz, which enabled response properties predicted for the optimized structure of each isomer to be combined through Boltzmann-weighted population fractions derived from corresponding relative internal-energy or free-energy values, the latter of which stemmed from composite CBS-APNO and G4 analyses. Although reasonable accord between theory and experiment was realized for the isolated (vapor-phase) species, the solution-phase results were less satisfactory and tended to degrade progressively as the solvent polarity increased. These trends were attributed to solvent-mediated changes in structural parameters and energy metrics for the transition states that separate and putatively isolate the equilibrium conformations supported by the ground electronic potential-energy surface, with the resulting displacement of barrier locations and/or decrease of barrier heights compromising the underlying premise of the independent-conformer ansatz.

Regulation of immune cell function by nicotinamide nucleotide transhydrogenase.

Redox homeostasis is elemental for the normal physiology of all cell types. Cells use multiple mechanisms to tightly regulate the redox balance. The onset and progression of many metabolic and aging-associated diseases occur due to the dysregulation of redox homeostasis. Thus, it is critical to identify and therapeutically target mechanisms that precipitate abnormalities in redox balance. Reactive oxygen species (ROS) produced within the immune cells regulate homeostasis, hyperimmune and hypoimmune cell responsiveness, apoptosis, immune response to pathogens, and tumor immunity. Immune cells have both cytosolic and organelle-specific redox regulatory systems to maintain appropriate levels of ROS. Nicotinamide nucleotide transhydrogenase (NNT) is an essential mitochondrial redox regulatory protein. Dysregulation of NNT function prevents immune cells from mounting an adequate immune response to pathogens, promotes a chronic inflammatory state associated with aging and metabolic diseases, and initiates conditions related to a dysregulated immune system such as autoimmunity. Although many studies have reported on NNT in different cell types, including cancer cells, relatively few studies have explored NNT in immune cells. This review provides an overview of NNT and focuses on the current knowledge of NNT in the immune cells.

Assessment of Functionality in Elderly Patients When Determining Appropriate Treatment for Nonmelanoma Skin Cancers.

BACKGROUND: The treatment of nonmelanoma skin cancer (NMSC) in the elderly population is a source of significant debate. Mohs micrographic surgery (MMS) is a highly effective treatment option yet not every patient with a cutaneous malignancy that meets appropriate use criteria (AUC) should be treated with surgery. OBJECTIVE: The purpose of this study was to use the Karnofsky Performance Status (KPS) scale to categorize the functional status of patients aged 75 years and older who required treatment of NMSC. The authors wanted to see whether functionality played a role on the treatment selection. METHODS: Patients aged 75 years and older presenting for biopsy of a suspected NMSC that met AUC for MMS were included in the study. Trained medical assistants used the KPS scale to assess patient functionality. Treatment modality was recorded once the biopsy confirmed the NMSC. RESULTS: A cohort of 203 subjects met inclusion criteria for the study. There was a statistically significant difference in utilization of surgical treatments between high and low functionality patients (p = .03). CONCLUSION: Dermatologists consider patient functionality when selecting a treatment for NMSC and use less invasive modalities for patients with poor functional status, even when the tumor meets AUC.

Comparison of poliglecaprone-25 and polyglactin-910 in cutaneous surgery.

BACKGROUND: Few clinical studies have compared deep absorbable sutures. Poliglecaprone-25 and polyglactin-910 are two of the most commonly used absorbable sutures in cutaneous surgery. OBJECTIVES: To compare the rate of suture extrusion, degree of lumpiness, and appearance of scars from wounds closed with poliglecaprone-25 and polyglactin-910. METHODS: Poliglecaprone-25 or polyglactin-910 was used for closure of the deep part of Mohs defects. The number of extruded sutures and the number of lumps were recorded at each follow-up visit. Photographs of 1-week and 3-month postoperative scars were rated on a visual analogue scale. RESULTS: One hundred forty patients completed the study. There was a statistically significant difference in the percentage of extruded sutures between poliglecaprone-25 (3.1%) and polyglactin-910 (11.4%) (p < .01). There was not a statistically significant difference in the percentage of lumps (both 22%) or overall appearance of scars at 1 week or 3 months. CONCLUSION: Poliglecaprone-25 resulted in significantly less extruded sutures than did polyglactin-910, although both resulted in the same degree of lumpiness and similar-appearing scars at 1 week and 3 months.

An unusual presentation of multiple hidrocystomas.

An 85-year-old man sought treatment of multiple nontender bluish papules of 3 years' duration on the forearms, forehead, and temples. On physical examination, blue-tinged, semitranslucent, dome-shaped papules were noted. Workup revealed multiple hidrocystomas. We discuss the findings in our patient and review the literature.

Depth of tissue ablation and residual thermal damage caused by a pixilated 2,940 nm laser in a swine skin model.

BACKGROUND/OBJECTIVE: The purpose of this study was to assess the effects of fluence, pulse stacking, and multiple passes on the depth of injury caused by a fractionated Er:YAG laser in an in vivo farm pig model. DESIGN/MATERIAL/METHODS: A fractionated 2,940 nm Er:YAG laser (Pixel, Alma Lasers, Caesarea, Israel) was applied to the flank skin of a Yorkshire cross pig. The 11 mmx11 mm handpiece was comprised of either 49 or 81 microbeams (200 microm diameter), depending on the tip configuration. There were six different parameter sets divided according to total energy per pulse (150, 285, and 500 mJ) and tip type (81 or 49 microbeams per 11 mmx11 mm macrospot). Each of these six groups was subdivided according to number of stacked pulses (1, 3, and 6) and number of passes (1, 3, and 6). This resulted in a total of 36 treatment parameters. RESULTS: With the 49 microbeam configuration, a single pulse resulted in partial epidermal ablation at 150 mJ, complete epidermal ablation at 285 mJ and partial dermal ablation at 500 mJ to a depth of 90 microm. Stacking the pulses resulted in a significant increase in ablation with each fluence with the maximal depth of ablation measured at 140 microm after six stacked pulses at 500 mJ. Increasing the number of passes did not result in a significant increase in ablative depth, but did create a larger surface area of ablation. Residual thermal damage (RTD) was minimal and remained between 10 and 20 microm. CONCLUSIONS: The fractionated Er:YAG laser exhibited some of the same tissue interactions as its fully ablative counterparts. An increase in fluence resulted in an increase in ablative depth with minimal RTD. Additionally, RTD was unaffected by pulse stacking or by additional passes. Differences were that pulse stacking appeared to yield a more rapid decrease in ablation efficiency and additional passes did not seem to increase the depth of ablation.

Taste comparison of corticosteroid suspensions.

OBJECTIVE: Although numerous taste studies have compared the palatability of antibiotic suspensions, few have compared the palatability of corticosteroid suspensions. Therefore, we compared the taste of 8 commonly prescribed liquid corticosteroid suspensions with the intent to help guide prescribing practices and improve patient compliance. METHODS: We conducted a randomized, double-blind study using 31 adult volunteers ages 24 to 57. All volunteers were asked to sample 8 different pediatric corticosteroid suspensions and to rate the palatability of their taste and aftertaste. The mean scores for each sample were then compared. RESULTS: The 8 suspensions fell into 2 groups based on their taste scores: one group with relatively high scores or more acceptable tastes (Orapred, Pediapred, and a dexamethasone suspension) and a second group with relatively low scores or less acceptable tastes (a prednisone suspension and 4 cherry-flavored prednisolone suspensions). CONCLUSIONS: The results demonstrate a significant difference in palatability between corticosteroid suspensions. Not only will this new information help clinicians choose between otherwise equivalent corticosteroid suspensions but, given the importance children place on taste, may improve compliance as well.

The scarring mechanism of smallpox.

BACKGROUND: Smallpox is notorious for leaving its survivors with disfiguring scars, but it is unclear how these scars are produced. Modern dermatopathology textbooks report that smallpox produced epidermal lesions, yet the process of scarring requires dermal involvement. OBJECTIVES: Our goal was to uncover past theories on the mechanism of smallpox scarring. METHODS: We conducted a comprehensive review of English-language textbooks and English-translations of textbooks in general medicine, dermatology, pathology, and dermatopathology from the past 150 years as well as relevant journal publications for the same time period. RESULTS: We identified five different theories to explain the scarring of smallpox. The five proposals are that scarring resulted from: the extension of suppuration into the dermis; the extension of suppuration into the dermis along with inappropriate treatment and scratching; secondary bacterial ecthyma; the destruction of elastic fibers; or the destruction of sebaceous glands. CONCLUSION: The theory that best fits clinical and histological observations is that smallpox caused scars through the destruction of sebaceous glands, first proposed by Gerrit Bras in 1952. Although this explanation is not found in any dermatopathology text, it is supported by today's leading authorities on smallpox. However, since variola virions have never actually been identified in sebaceous glands, or even in the dermis, further study of preserved tissue is warranted. Until then, the mechanism of scar formation remains speculative.