Preauricular Aging: A Three-Point Grading System to Guide Treatment in Facial Rejuvenation.

BACKGROUND: Aging affects the face in all its dimensions. However, more has been published about the improvement of the periocular, midface, and perioral aging changes. We believe the profile view, particularly the preauricular area, is of great value when assessing the need for facial contouring procedures, as well as their effectiveness. OBJECTIVE: To develop and evaluate a classification based on the aging changes around the preauricular area, which aims to provide an objective direction to the appropriate treatment method. METHODS AND MATERIALS: All patients who attended the clinic for different aesthetic procedures between June 2019 and January 2020 were photographed. Two non-treating dermatologists and two non-treating plastic surgeons were asked to evaluate the perceived aging of the preauricular area using a three-point grading system. The assessment of each photograph was made once by each evaluator, and the inter-rater correlation was calculated. RESULTS: A total of 158 profile pictures of the preauricular area of 158 patients were evaluated by two non-treating dermatologists and two non-treating plastic surgeons. The inter-rater correlation was excellent at 0.942. The mean grading system of the patient samples was 1.42, with a standard deviation of 0.9 and a variance of 0.001. CONCLUSIONS: The preauricular area is often overlooked and undertreated. Our results demonstrate an excellent inter-rater correlation between plastic surgeons and dermatologists at assessing the degree of aging in the area. This relatively hidden lateral area can serve as a test point, evaluating response to selected treatment before proceeding to full-face intervention. We suggest using a simple three-point scale to help guide treatment of the preauricular area and as part of our holistic approach to facial rejuvenation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Failure in a Liver Transplant Patient: A Case Report.

Intraoperative extracorporeal membrane oxygenation (ECMO) support, both venoarterial and venovenous (VV), have been used sparingly and with limited success in the setting of liver transplantation. Here, we report the successful use of VV-ECMO in the resuscitation and pulmonary bridging support after severe systemic inflammatory response in a combined liver and kidney transplant recipient who suffered primary nonfunction of both allografts. Where conventional ventilator maneuvers may prove ineffective, the implementation of VV-ECMO should be considered as a therapeutic option in limited, short-lived acute pulmonary injury.

Rat Hindlimb Cryopreservation and Transplantation: A Step Toward "Organ Banking".

In 2016, over 5 million reconstructive procedures were performed in the United States. The recent successes of clinical vascularized composite allotransplantations, hand and face transplantations included, established the tremendous potential of these life-enhancing reconstructions. Nevertheless, due to limited availability and lifelong immunosuppression, application is limited. Long-term banking of composite transplants may increase the availability of esthetically compatible parts with partial or complete HLA matching, reducing the risk of rejection and the immunosuppressive burden. The study purpose was to develop efficient protocols for the cryopreservation and transplantation of a complete rodent limb. Directional freezing is a method in which a sample is cooled at a constant-velocity linear temperature gradient, enabling precise control of the process and ice crystal formation. Vitrification is an alternative cryopreservation method in which the sample solidifies without the formation of ice crystals. Testing both methods on a rat hindlimb composite tissue transplantation model, we found reliable, reproducible, and stable ways to preserve composite tissue. We believe that with further research and development, cryopreservation may lead to composite tissue "banks." This may lead to a paradigm shift from few and far apart emergent surgeries to wide-scale, well-planned, and better-controlled elective surgeries.

NOX1-induced accumulation of reactive oxygen species in abdominal fat-derived mesenchymal stromal cells impinges on long-term proliferation.

Mesenchymal stromal cells (MSCs) are multipotent and can be derived from different adult tissues including fat. Our repeated attempts to produce long-term proliferative cultures of rat abdominal adipose stem cells (aASCs) under normal oxygen concentration (21%) were unsuccessful. We set to examine the events controlling this cytostasis of aASCs and found that it resulted from overproduction of reactive oxygen species (ROS) that led to apoptosis. ROS overproduction in aASCs was accompanied by increased expression of NOX1 but not of NOX2 or NOX4. NOX family members are an important source of intracellular ROS pointing to NOX1 involvement in ROS accumulation. This was verified when aASCs that were grown under 3% oxygen conditions expanded long term, displaying reduced NOX1 expression and decreased ROS accumulation. NOX1 involvement in aASC cytostasis was reaffirmed when cells that were expanded under normoxic conditions in the presence of a specific NOX1 inhibitor, ML171, demonstrated reduced ROS accumulation, reduced apoptosis and long-term expansion. aASC expansion arrest was accompanied also by a weak fat differentiation and migratory potential, which was enhanced by NOX1 inhibition. This suggests an inhibitory role for NOX1-induced ROS overproduction on aASCs, their fat differentiation and migratory potential. In contrast to aASCs, similar cells produced from subcutaneous fat were easily expanded in normoxic cultures, exhibiting low ROS concentrations, a low number of apoptotic cells and improved fat differentiation and migration. Taken together, our results show, for the first time, that NOX1-induced ROS accumulation halts ASC expansion and reduces their differentiation and migratory potential under normoxic conditions. Importantly, this phenotype comprises a tissue-specific signature as it was evident in aASCs but not in subcutaneous ASCs. NOX-induced ROS accumulation and cytokine production by fat are part of the metabolic syndrome. The similarity of this phenomenon to aASC phenotype may indicate that they arise from similar molecular mechanisms.

Catheter-directed clot fragmentation using the Cleaner™ device in a patient presenting with massive pulmonary embolism.

Massive pulmonary embolism not amenable to systemic thrombolysis is a therapeutic challenge. Catheter directed clot fragmentation and thrombolysis have been efficacious in this setting. We describe successfully treating a massive pulmonary embolism with catheter-directed thrombolysis and clot fragmentation using local tPA, aspiration, and the Cleaner™ device in a patient with an absolute contraindication to systemic thrombolysis.

Azathioprine and diffuse alveolar haemorrhage: the pharmacogenetics of thiopurine methyltransferase.

Current guidelines support the use of corticosteroids and azathioprine as one possible treatment strategy for idiopathic pulmonary fibrosis (IPF). However, some patients with genetic polymorphisms of thiopurine methyltransferase (TPMT) are at risk of severe azathioprine myelotoxicity. The current authors present the case of an 85-yr-old Caucasian male with IPF who developed diffuse alveolar haemorrhage as a complication of azathioprine-induced myelosuppression. Leukocyte genetic TPMT testing revealed that the patient had homozygous polymorphisms associated with the absence of TPMT activity and severe azathioprine-induced myelotoxicity. Thiopurine methyltransferase deficiency should be considered in patients who develop leukopenia early in treatment with azathiopurine, or who present with severe marrow suppression at usual doses. For centres with equipped laboratories, a dosing suggestion is provided based on thiopurine methyltransferase testing. Even with screening strategies, frequent monitoring of complete blood count and liver biochemistry should remain the mainstay of surveillance for azathioprine toxicity.

Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex.

Disruption of the blood-brain barrier (BBB) is a characteristic finding in common neurological disorders. Human data suggest BBB disruption may underlie cerebral dysfunction. Animal experiments show the development of epileptiform activity following BBB breakdown. In the present study we investigated the neurophysiological, structural and functional consequences of BBB disruption. Adult rats underwent focal BBB disruption in the rat sensory-motor cortex using the bile salt sodium deoxycholate (DOC). Magnetic resonance imaging in-vivo showed an early BBB disruption with delayed reduction in cortical volume. This was associated with a reduced number of neurons and an increased number of astrocytes. In-vitro experiments showed that the threshold for spreading depression and the propagation velocity of the evoked epileptic potentials were increased 1 month after treatment. Furthermore, animals' motor functions deteriorated during the first few weeks following BBB disruption. Treatment with serum albumin resulted in a similar cell loss confirming that the effect of DOC was due to opening of the BBB. Our findings suggest that delayed neurodegeneration and functional impairment occur following the development of the epileptic focus in the BBB-permeable cerebral cortex.

Acute and fatal hyponatraemia after resection of a craniopharyngioma: a preventable tragedy.

Central diabetes insipidus developed for the first time in a 14-year-old female during the resection of a craniopharyngioma. The water diuresis persisted until a vasopressin analogue (dDAVP) was given. Professor McCance was asked to explain why hypernatraemia developed, to anticipate dangers that might develop in the salt and water area with therapy, and to provide insights into why this patient died, due to the subsequent development of hyponatraemia that caused a lethal rise in intracranial pressure. The team specifically wanted Professor McCance's opinions as to why a PNa of 124 mmol/l was uniquely dangerous for this patient, and this was a particularly challenging conundrum. Nevertheless, with the aid of a mini-experiment, a careful chart review, and creative thinking, he was able to offer a novel solution, and to suggest ways to prevent its occurrence in other patients.

Xanthoma of the temporal bone: a unique case of this rare condition.

Xanthoma of the temporal bone is extremely rare; we describe only the fourteenth reported case. Our case is further remarkable because it is the first report of such an occurrence in a patient with familial type III hyperlipoproteinemia. Moreover, while otalgia, infection, hearing loss, and tinnitus were the most common initial symptoms in the previous 13 cases, our patient reported only diplopia, vertigo, and unstable gait. The patient underwent a simple mastoidectomy and debulking, and his diplopia, vertigo, and unstable gait resolved.

[Folic acid use by pregnant women in Israel for preventing neural tube defects].

Spina bifida and anencephaly are the most common, serious malformations in neural tube defects (NTD). Randomized trials in the last 2 decades have demonstrated that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We investigated the use of folic acid and multivitamins containing folic acid in childbearing women. Of 221 women interviewed, 67 (30%) regularly took pills containing 0.4 mg folic acid. Women with higher educational levels were more likely to take multivitamins with folic acid than were the less educated (p = 0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid tablets, before and during their pregnancy. The rest used multivitamins containing folic acid. The 5 women who took folic acid separately were college-educated and nonreligious, and they took multivitamins in addition (p > 0.05). Of the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them took pills containing folic acid on a regular basis. This percentage is higher than that in the Jewish women in the study who took folic acid for prevention of NTD (17%; p = 0.038). Most of the women took folic acid after the first trimester. Only a minority took daily periconceptional folic acid. Multivitamins containing 0.4 mg of folic acid were more popular than folic acid tablets alone. This study emphasizes the need for continuing efforts to increase consumption of folic acid and awareness of its benefits among women of childbearing age.

Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family.

LXR and PPAR receptors belong to the nuclear receptor superfamily of transcriptional activating factors. Using ligand-dependent transcription assays, we found that 5-tetradecyloxy-2-furancarboxylic acid (TOFA) transactivates chimeric receptors composed of the glucocorticoid receptor DNA binding domain and the ligand binding regions of PPARalpha, PPARbeta (NUC-1) and LXRbeta (NER) receptors. In the same assays, ligands for PPARs (oleic acid, WY-14643 and L-631,033) and LXRs (hydroxycholesterols) maintain their respective receptor selectivity. TOFA and hydroxycholesterols also stimulate transcription from a minimal fibrinogen promoter that is under the control of AP-1 or NF-kappaB transcription factor binding sites. In addition to their effects on transcription, these LXRbeta activators induce neuronal differentiation in rat pheochromocytoma cells. TOFA and the natural LXR agonist, 22 (R)-hydroxycholesterol, stimulate neurite outgrowth in 55 and 28% of cells, respectively. No neurite outgrowth was induced by the related 22(S)-hydroxycholesterol, which does not activate the LXR family. These results suggest that the hydroxycholesterol signaling pathway has a complex effect on transcription that mediates the activity of TOFA and hydroxycholesterol on neuronal differentiation in pheochromocytoma cells.

Postoperative bilevel positive airway pressure ventilation after tonsillectomy and adenoidectomy in children--a preliminary report.

Obstructive sleep apnea (OSA) in children, characterized by hypoventilation secondary to upper airway obstruction, often results from tonsil and adenoid hypertrophy. Adenotonsillectomy is the standard therapy in this patient population. The immediate postoperative period is complicated occasionally by respiratory difficulties that may require intubation and mechanical ventilation. Recently, physicians have provided temporary airway support using continuous and bilevel positive airway pressure (BiPAP) devices. Reported complications of positive airway pressure devices include local abrasions to the nose and mouth; dryness of the nose, eyes, and mouth; sneezing; nasal drip, bleeds, and congestion; sinusitis; increased intraocular pressure; non-compliance; and pneumocephalus. Subcutaneous emphysema following facial trauma, dental extractions, adenotonsillectomy, and sinus surgery has been reported. There is also a hypothetically increased risk of subcutaneous emphysema following the use of positive airway pressure ventilation in the tonsillectomy patient. Between January 1997 and July 1998, 1321 patients underwent tonsillectomy and/or adenoidectomy at our institution. In reviewing the records of all pediatric intensive care unit admissions during that time period, we identified nine patients, of the 1321, who required BiPAP postoperatively. Of these, four children were obese, four had preexisting neurological disorders, and one underwent endoscopic sinus surgery and adenoidectomy. Three children were asthmatic, and three were less than 3 years of age. Two obese children were discharged with home BiPAP, one of whom had been on BiPAP prior to surgery. All patients tolerated BiPAP without complications. This preliminary report suggests that BiPAP is a safe and effective method of respiratory assistance in the adenotonsillectomy patient with preexisting conditions who is predisposed to postoperative airway obstruction. Furthermore, with BiPAP, the risks of intubation and ventilator dependence are avoided.

Effect of Nitrogen on Polysaccharide Production in a Porphyridium sp.

Porphyridium cultures grown on either nitrate or ammonium as the nitrogen source showed similar patterns of growth and cell wall polysaccharide production. The effect of nitrogen on growth and cell wall polysaccharide production was studied by applying three regimens of supply: batch mode, in which nitrate was supplied at the beginning of the experiment and became depleted at day 6; continual mode, in which nitrate was added daily; and deficient mode, in which the cells were cultured in a nitrate-free medium. Growth was similar in the batch- and continual-mode cultures, whereas it was totally inhibited in the deficient-mode culture. Polysaccharide content (per volume) was highest in the batch-mode culture and lowest in the deficient-mode culture. However, polysaccharide production per cell was similar in the continual- and deficient-mode cultures, the highest value being found in the batch-mode culture. In addition to its effect on polysaccharide content, nitrogen affected the polysaccharide distribution between soluble and bound polysaccharides. In the deficientmode culture, most of the cell wall polysaccharide was dissolved in the medium.

Iminocyclophosphamide as a chemically reactive metabolite of cyclophosphamide.

Iminocyclophosphamide has been identified among the metabolites produced by incubation of cyclophosphamide with cytochrome P-450 mono-oxygenase immobilized on beaded Sepharose. The reactive imine was trapped by addition of hydrogen cyanide, and the product, 4-cyanocyclophosphamide, was identified by comparison of its chromatographic and mass-spectral properties with those of a synthetic standard. Iminocyclophosphamide was also generated chemically from 4-hydroperoxycyclophosphamide and characterized both by addition of hydrogen cyanide and by reduction with sodium borodeuteride. The synthesis of authentic 4-cyanocyclophosphamide is also reported.

Identification of aldophosphamide as a metabolite of cyclophosphamide in vitro and in vivo in humans.

Aldophosphamide (NSC 254), a putative key metabolite of cyclophosphamide, has now been isolated as a cyanohydrin derivative from an incubation mixture of cyclophosphamide with mouse liver microsomes in vitro and from the plasma of a cyclophosphamide-treated patient. The cyanohydrin has been shown to be identical with an authenic synthetic sample by mass spectrometry and combined gas chromatography-mass spectrometry.