DRMref: comprehensive reference map of drug resistance mechanisms in human cancer.

Drug resistance poses a significant challenge in cancer treatment. Despite the initial effectiveness of therapies such as chemotherapy, targeted therapy and immunotherapy, many patients eventually develop resistance. To gain deep insights into the underlying mechanisms, single-cell profiling has been performed to interrogate drug resistance at cell level. Herein, we have built the DRMref database (https://ccsm.uth.edu/DRMref/) to provide comprehensive characterization of drug resistance using single-cell data from drug treatment settings. The current version of DRMref includes 42 single-cell datasets from 30 studies, covering 382 samples, 13 major cancer types, 26 cancer subtypes, 35 treatment regimens and 42 drugs. All datasets in DRMref are browsable and searchable, with detailed annotations provided. Meanwhile, DRMref includes analyses of cellular composition, intratumoral heterogeneity, epithelial-mesenchymal transition, cell-cell interaction and differentially expressed genes in resistant cells. Notably, DRMref investigates the drug resistance mechanisms (e.g. Aberration of Drug's Therapeutic Target, Drug Inactivation by Structure Modification, etc.) in resistant cells. Additional enrichment analysis of hallmark/KEGG (Kyoto Encyclopedia of Genes and Genomes)/GO (Gene Ontology) pathways, as well as the identification of microRNA, motif and transcription factors involved in resistant cells, is provided in DRMref for user's exploration. Overall, DRMref serves as a unique single-cell-based resource for studying drug resistance, drug combination therapy and discovering novel drug targets.

Interneuron Origins in the Embryonic Porcine Medial Ganglionic Eminence.

Interneurons contribute to the complexity of neural circuits and maintenance of normal brain function. Rodent interneurons originate in embryonic ganglionic eminences, but developmental origins in other species are less understood. Here, we show that transcription factor expression patterns in porcine embryonic subpallium are similar to rodents, delineating a distinct medial ganglionic eminence (MGE) progenitor domain. On the basis of Nkx2.1, Lhx6, and Dlx2 expression, in vitro differentiation into neurons expressing GABA, and robust migratory capacity in explant assays, we propose that cortical and hippocampal interneurons originate from a porcine MGE region. Following xenotransplantation into adult male and female rat hippocampus, we further demonstrate that porcine MGE progenitors, like those from rodents, migrate and differentiate into morphologically distinct interneurons expressing GABA. Our findings reveal that basic rules for interneuron development are conserved across species, and that porcine embryonic MGE progenitors could serve as a valuable source for interneuron-based xenotransplantation therapies.SIGNIFICANCE STATEMENT Here we demonstrate that porcine medial ganglionic eminence, like rodents, exhibit a distinct transcriptional and interneuron-specific antibody profile, in vitro migratory capacity and are amenable to xenotransplantation. This is the first comprehensive examination of embryonic interneuron origins in the pig; and because a rich neurodevelopmental literature on embryonic mouse medial ganglionic eminence exists (with some additional characterizations in other species, e.g., monkey and human), our work allows direct neurodevelopmental comparisons with this literature.

Sleep Quality Improvement Enhances Neuropsychological Recovery and Reduces Blood Aß42/40 Ratio in Patients with Mild-Moderate Cognitive Impairment.

Background and objectives: Alzheimer's disease is a progressive brain degeneration and is associated with a high prevalence of sleep disorders. Amyloid ß peptide-42/40 (Aß42/40) and Tau-pT181 are the core biomarkers in cerebrospinal fluid and blood. Accumulated data from studies in mouse models and humans demonstrated an aberrant elevation of these biomarkers due to sleep disturbance, especially sleep-disordered breathing (SDB). However, it is not clear if sleep quality improvement reduces the blood levels of Ab42/40 ratio and Tau-pT181 in Alzheimer's disease patients. Materials and Methods: In this prospective study, a longitudinal analysis was conducted on 64 patients with mild-moderate cognition impairment (MCI) due to Alzheimer's disease accompanied by SDB. Another 33 MCI cases without sleep-disordered breathing were included as the control group. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) score system. Neuropsychological assessments were conducted using the Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Clinical Dementia Rating (CDR), 24-h Hamilton Rating Scale for Depression (HRSD-24), and Hamilton Anxiety Rating Scale (HAMA) scoring systems. Aß42, Aß40, and Tau-pT181 protein levels in blood specimens were measured using ELISA assays. All patients received donepezil treatment for Alzheimer's disease. SDB was managed with continuous pressure ventilation. Results: A significant correlation was found among PSQI, HRSD-24, HAMA, Aß42/40 ratio, and Tau-pT181 level in all cases. In addition, a very strong and negative correlation was discovered between education level and dementia onset age. Compared to patients without SDB (33 non-SD cases), patients with SDB (64 SD cases) showed a significantly lower HRSD-24 score and a higher Aß42/40 ratio Tau-pT181 level. Sleep treatment for patients with SDB significantly improved all neuropsychological scores, Aß42/40 ratio, and Tau-pT181 levels. However, 11 patients did not completely recover from a sleep disorder (PSQI > 5 post-treatment). In this subgroup of patients, although HAMA score and Tau-pT181 levels were significantly reduced, MoCA and HRSD-24 scores, as well as Aß42/40 ratio, were not significantly improved. ROC analysis found that the blood Aß42/40 ratio held the highest significance in predicting sleep disorder occurrence. Conclusions: This is the first clinical study on sleep quality improvement in Alzheimer's disease patients. Sleep quality score was associated with patient depression and anxiety scores, as well as Aß42/40 ratio and Tau-pT181 levels. A complete recovery is critical for fully improving all neuropsychological assessments, Aß42/40 ratio, and Tau-pT181 levels. Blood Aß42/40 ratio is a feasible prognostic factor for predicting sleep quality.

Spontaneous subperiosteal orbital hematoma as initial presentation of metastatic lung adenocarcinoma to the skull: case report.

INTRODUCTION: Subperiosteal orbital hematoma is a rare occurrence, typically developing as a result of orbital trauma. The spontaneous formation of a subperiosteal orbital hematoma (sSOH) may also occur but is less frequent. To date there has been no documented cases of sSOH as the initial presentation of an unknown metastatic neoplasm to the skull. We provide a case of a woman with unknown lung adenocarcinoma that metastasized to the skull which caused the formation of a sSOH resulting in orbital compression syndrome. CASE REPORT: A 57-year-old female presented with double vision, retro-orbital right eye pain, and vision loss in the right eye. A magnetic resonance imaging revealed a right orbital compressive lesion with an adjacent supraorbital skull lesion and separate left frontal skull lesion. Intra-operative findings along with post-operative immunohistochemistry staining revealed sSOH resulting from a metastatic lung adenocarcinoma to the skull. Further metastatic work up also revealed an occult lung mass and multiple spinal lesions. CONCLUSION: Differential diagnosis of etiologies causing the formation of sSOH in an adult without history of trauma should include metastatic neoplasm to the skull and warrants metastatic workup. Treatment options of sSOH have included observation with spontaneous resolution; however, we opted for surgical decompression of the eye and biopsy of the skull mass.

Insights from the AQUA Registry: a retrospective study of anticholinergic polypharmacy in the United States.

Background: Anticholinergic (ACH) burden is a risk factor for negative health outcomes among older adults. Several medications contribute to ACH burden, including antimuscarinics used to manage overactive bladder (OAB). Objectives: This study aimed to understand the extent of ACH burden in an OAB population in the United States. Design: Non-interventional retrospective analysis. Methods: Adults with OAB whose care providers participated in the American Urological Association Quality (AQUA) Registry between 2014 and 2020 were included in this study. An adapted version of the Pharmacy Quality Alliance (PQA) measure of anticholinergic polypharmacy (poly-ACH) was used to assess ACH burden. The primary outcome was the annual prevalence of poly-ACH, and a secondary outcome was the percentage of patients taking 0, 1, 2, 3, 4, or ⩾ 5 ACH medications by calendar year. Analyses were stratified by age category at diagnosis and sex. Results: The sample comprised 552,840 patients with OAB. The mean age at initial OAB diagnosis was 65.7 years (58.2% male; 57.4% white). Prevalence of poly-ACH was highest in 2015 (3.7%) and lowest in 2020 (1.9%). Patients prescribed no ACH medications made up the largest proportion of each cohort, while those prescribed five or more comprised the smallest. The trend of decreasing proportions of patients taking increasing numbers of ACH medications was consistent. The proportion of patients prescribed no ACH medications increased from 63.3% in 2014 to 74.6% in 2020. The percentage of those prescribed three or more ACHs remained largely unchanged. Poly-ACH was highest among younger individuals (< 65 years of age) and females; temporal trends were similar overall and within each age and sex stratum. Conclusion: In this study, poly-ACH in patients with OAB was relatively infrequent and decreased over the study period. Further evaluation of poly-ACH is needed to assess whether the study findings reflect increased awareness of the negative effects of poly-ACH.

A Retrospective Chart Review of Treatment Patterns and Overall Survival among a Cohort of Patients with Relapsed/Refractory Mycosis Fungoides in France, Germany, Italy, Spain and the United Kingdom.

(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lymphoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analyzed patient records (1984-2016) from 27 clinical sites in Europe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS) and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. The median (range) times from the start of first-line therapy to the first R/R MF and from the first to the second R/R MF were 11.2 (0.3-166.5) and 13.5 (0.0-174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radiotherapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). The median (95% confidence interval [CI]) OS from the diagnosis of the first R/R MF was 11.5 (6.5-not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); the estimated median PFS (95% CI) from the time of the first R/R MF was 1.3 (1.0-2.1) years. (4) Conclusions: High rates of R/R disease were observed after second- and third-line treatments in this real-world cohort, with longer median OS in patients receiving non-chemotherapy treatment versus chemotherapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.

Pregnancy outcomes in women with active anorexia nervosa: a systematic review.

BACKGROUND: It is a common misconception that women with active anorexia nervosa (AN) are less likely to conceive. Pregnancies in women with AN are considered high risk. The purpose of this systematic review was to explore pregnancy complications in women with active AN, including maternal, fetal, and neonatal complications. METHODS: The authors conducted a systematic review in accordance with PRISMA statement guidelines with stringent selection criteria to include studies on patients with active AN during pregnancy. RESULTS: There were 21 studies included in our review. Anaemia, caesarean section, concurrent recreational substance use, intrauterine growth restriction, preterm birth, small-for-gestation (SGA) birth, and low birth weight were the most reported pregnancy complications in women with active AN, while the rates of gestational diabetes and postpartum haemorrhage were lower. DISCUSSION: Women with active AN have a different profile of pregnancy complications comparing to malnourished women and women in starvation. We recommend early discussion with women diagnosed with AN regarding their fertility and pregnancy complications. We recommend clinicians to aim to improve physical and psychological symptoms of AN as well as correction of any nutritional deficiency ideally prior to conception. Management of pregnancies in women with active AN requires regular monitoring, active involvement of obstetricians and psychiatrist. Paediatric follow-up postpartum is recommended to ensure adequate feeding, wellbeing and general health of the infants. Psychiatric follow-up is recommended for mothers due to risk of worsening symptoms of AN during perinatal period.

It is a common myth that women with active anorexia nervosa are less likely to become pregnant. Generally, pregnancies in women with active anorexia nervosa are considered high risk. This review looked at pregnancy complications in women with active anorexia nervosa that affect the mothers as well as unborn and newborn babies. There are number of complications reported, most commonly, anaemia, increased chance of birth by C-section, increased risk of substance use in mothers, poor growth of unborn babies, and smaller babies at birth. Mothers with anorexia nervosa are less likely to suffer from pregnancy related diabetes and postpartum haemorrhage. Interestingly, women with active anorexia nervosa tend to have different pregnancy complications comparing to women without adequate nutrition and women in starvation. It is important to mention that although women with anorexia nervosa carry higher risk of complications during pregnancy, the risk can be reduced with the help of obstetricians and psychiatrists. After birth, paediatrician visits can help identify any issue with the baby. Symptoms of anorexia nervosa could potentially get worse after delivering a baby. It is important to continue regular visits to a psychiatrist.

Pyridine-derived γ-secretase modulators.

SAR of a novel series of pyridine-derived γ-secretase modulators is described. Compound 5 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aß42 and Aß40, and maintain (or increase) the levels of total Aß. Furthermore, representative compounds 1 and 5 demonstrated in vivo efficacy to lower Aß42 in the brain without altering Notch processing in the peripheral.

Hippocampal gamma and sharp-wave ripple oscillations are altered in a Cntnap2 mouse model of autism spectrum disorder.

Impaired synaptic neurotransmission may underly circuit alterations contributing to behavioral autism spectrum disorder (ASD) phenotypes. A critical component of impairments reported in somatosensory and prefrontal cortex of ASD mouse models are parvalbumin (PV)-expressing fast-spiking interneurons. However, it remains unknown whether PV interneurons mediating hippocampal networks crucial to navigation and memory processing are similarly impaired. Using PV-labeled transgenic mice, a battery of behavioral assays, in vitro patch-clamp electrophysiology, and in vivo 32-channel silicon probe local field potential recordings, we address this question in a Cntnap2-null mutant mouse model representing a human ASD risk factor gene. Cntnap2-/- mice show a reduction in hippocampal PV interneuron density, reduced inhibitory input to CA1 pyramidal cells, deficits in spatial discrimination ability, and frequency-dependent circuit changes within the hippocampus, including alterations in gamma oscillations, sharp-wave ripples, and theta-gamma modulation. Our findings highlight hippocampal involvement in ASD and implicate interneurons as a potential therapeutical target.

Working with Young People at Risk of Suicidal Behaviour and Self-Harm: A Qualitative Study of Australian General Practitioners' Perspectives.

General Practitioners (GPs) play a crucial role in the identification and support of young people at risk of suicidal behaviour and self-harm; however, no studies have explored GPs' perspectives, approaches, challenges, and resource needs when working with this cohort in an Australian setting. This was a qualitative study where fifteen GPs (Mage = 45.25 years) from multiple clinics in Western Australia took part in semi-structured interviews, and data were analysed thematically. Seven main themes were identified: (1) working with young people has its unique challenges; (2) screening and assessment tools can help to manage uncertainty and discomfort; (3) going beyond tools-the dialogue and relationship are most important; (4) there are limits to what we can offer in the time available; (5) the service access and referral pathways lack clarity and coordination; (6) the provision of mental health support should not fall on GPs alone; and (7) more comprehensive training in suicide and self-harm is needed. The findings highlight a number of opportunities to enhance care and better assist GPs working with young people who present with suicidal behaviour and self-harm, including considerations for conducting assessments, targeted resources such as training, and system and service improvements.

Contemporary Treatment Patterns and Response in Relapsed/Refractory Cutaneous T-Cell Lymphoma (CTCL) across Five European Countries.

The treatment pattern of cutaneous T-cell lymphoma (CTCL) remains diverse and patient-tailored. The objective of this study was to describe the treatment patterns and outcomes in CTCL patients who were refractory or had relapsed (R/R) after a systemic therapy. A retrospective chart review study was conducted at 27 sites in France, Germany, Italy, Spain and the United Kingdom (UK) of patients who received a first course of systemic therapy and relapsed or were refractory. Data were collected longitudinally from diagnosis to first-, second- and third-line therapy. The study included 157 patients, with a median follow-up of 3.2 years. In total, 151 proceeded to second-line and 90 to third-line therapy. In the first line (n = 147), patients were treated with diverse therapies, including single- and multi-agent chemotherapy in 67 (46%), retinoids in 39 (27%), interferon in 31 (21%), ECP in 4 (3%), corticosteroids in 3 (2%) and new biological agents in 3 (2%). In the second line, the use of chemotherapy and retinoids remained similar to the first line, while the use of new biologics increased slightly. In sharp contrast to the first line, combination chemotherapy was extremely diverse. In the third line, the use of chemotherapy remained high and diverse as in the second line. From the time of first R/R, the median PFS was 1.2 years and the median OS was 11.5 years. The presented real-world data on the current treatments used in the management of R/R CTCL in Europe demonstrate the significant heterogeneity of systemic therapies and combination therapies, as expected from the European guidelines.

Ni(III)/(IV) bis(dicarbollide) as a fast, noncorrosive redox shuttle for dye-sensitized solar cells.

Nickel bis(dicarbollide) is used as a fast, one-electron outer sphere redox couple in dye-sensitized solar cells. Device performances with this anionic shuttle are investigated with different electrolyte concentrations and additives, using only 0.030 M of the Ni(III) bis(dicarbollide) to efficiently regenerate the ruthenium dye. Atomic layer deposition of Al(2)O(3) on the nanoparticulate TiO(2) photoanodes is further used to improve device performances, increasing current densities almost 2-fold and attaining power conversion efficiencies approximately 10x greater than its metallocene analogue, ferrocene/ferrocenium. Open-circuit voltage decay is used to probe the kinetics of the Ni(III)/(IV) bis(dicarbollide) redox couple, and electron interception is found to be approximately 10(3)x slower than ferrocene/ferrocenium, explaining the large discrepancy in open-circuit voltage potentials between these two redox shuttles.

Best practice when working with suicidal behaviour and self-harm in primary care: a qualitative exploration of young people's perspectives.

OBJECTIVES: General practitioners (GPs) have a key role in supporting young people who present with suicidal behaviour/self-harm. However, little is known about young people's opinions and experiences related to GPs' practices for such presentations, and their decisions to disclose suicidal behaviour/self-harm to GPs. Additionally, existing guidelines for the management of suicide risk and/or self-harm have not incorporated young people's perspectives. This study aimed to explore young people's views and experiences related to the identification, assessment and care of suicidal behaviour and self-harm in primary care settings with GPs. DESIGN, SETTING AND PARTICIPANTS: Two qualitative focus groups were conducted in Perth, Western Australia, with 10 young people in total (Mage = 20.67 years; range: 16-24). Data were collected using a semistructured, open-ended interview schedule and analysed using thematic analysis. RESULTS: Five major themes were identified from the focus groups. (1) Young people wanted a collaborative dialogue with GPs, which included being asked about suicidal behaviour/self-harm, informed of treatment processes and having autonomy in decision making; (2) young people were concerned with a loss of privacy when disclosing suicidal behaviour/self-harm; (3) young people viewed labels and assessments as problematic and reductionist-disliking the terms 'risk' and 'risk assessment', and assessment approaches that are binary and non-holistic; (4) young people highlighted the importance of GPs' attitudes, with a genuine connection, attentiveness and a non-judgemental demeanour seen as paramount; and (5) young people wanted to be provided with practical support and resources, followed-up, and for GPs to be competent when working with suicidal behaviour/self-harm presentations. CONCLUSIONS: Our study identified several concerns and recommendations young people have regarding the identification, assessment and care of suicidal behaviour/self-harm in primary care settings. Taken together, these findings may inform the development of resources for GPs, and support progress in youth-oriented best practice.

Characteristics of non-randomised studies using comparisons with external controls submitted for regulatory approval in the USA and Europe: a systematic review.

OBJECTIVES: Non-randomised clinical trial designs involving comparisons against external controls or specific standards can be used to support regulatory submissions for indications in diseases that are rare, with high unmet need, without approved therapies and/or where placebo is considered unethical. The objective of this review was to summarise the characteristics of non-randomised trials submitted to the European Medicines Agency (EMA) or Food and Drug Administration (FDA) for indications in haematological cancers, haematological non-malignant conditions, stem cell transplants or rare metabolic diseases. METHODS: We conducted systematic searches of EMA databases of conditional approvals, exceptional circumstances, or orphan drug designations and FDA inventories of orphan drug designations, accelerated approvals, breakthrough therapy, fast-track and priority approvals. Products were included if reviewed by at least one agency between 2005 and 2017, the primary evidence base was non-randomised trial(s) and the indication was for haematological cancers, stem cell transplantation, haematological conditions or rare metabolic conditions. RESULTS: We identified 43 eligible indication-specific products using non-randomised study designs involving comparisons with external controls, submitted to the EMA (n=34) and/or FDA (n=41). Of the 43 indication-specific products, 4 involved matching external controls to the population of a non-randomised interventional study using individual patient-level data (IPD), 12 referred to external controls without IPD and 27 did not explicitly reference external controls. The FDA approved 98% of submissions, with 56% accelerated approvals; most required postapproval confirmatory randomised controlled trials (RCT). The EMA approved 79% of submissions, with a quarter of approvals conditional on completion of a postapproval RCT or additional non-randomised trials. CONCLUSIONS: There has been a large increase in submissions to the EMA and FDA using non-randomised study designs involving comparisons with external controls in recent years. This study demonstrated that regulators may be willing to approve such submissions, although approvals are often conditional on further confirmatory evidence from postapproval studies.

Novel rechargeable nano-CaF2 orthodontic cement with high levels of long-term fluoride release.

OBJECTIVES: Fluoride-containing orthodontic cements are used to combat white spot lesions (WSLs) in enamel. However, the fluoride (F) ion releases from these cements are relatively low and short-term. The objectives of this study were to develop a novel rechargeable orthodontic cement with nanoparticles of calcium fluoride (nCaF2) to provide long-term and high levels of F release, and to investigate F recharge and physical and cytotoxic properties. METHODS: The nCaF2 with a mean particle size of 58 nm were synthesized using a spray-drying method. Pyromellitic glycerol dimethacrylate (PMGDM), ethoxylated bisphenol A dimethacrylate (EBPADMA), 2-hydroxyethyl methacrylate (HEMA) and bisphenol A glycidyl dimethacrylate (BisGMA) were used to prepare the cements (denoted PE and PEHB resins). A resin-modified glass ionomer (RMGI) served as control. Enamel shear bond strength (SBS), cytotoxicity, and F ion recharge and re-release were evaluated. RESULTS: nCaF2 cements had good SBS and excellent biocompatibility that were comparable to RMGI (p > 0.1). After a recharge for 1 min, the F re-release from PEHB + 30%nCaF2 cement was 80% higher than RMGI (p < 0.05). Increasing nCaF2 content from 20% to 30% greatly increased the F ion re-release (p < 0.05). The F ion re-release of nCaF2 cements did not decrease with increasing the number of recharge and re-release cycles (p > 0.1). CONCLUSIONS: A novel F ion-rechargeable orthodontic cement containing nCaF2 was developed with clinically acceptable enamel SBS, good biocompatibility, and sustained F ion recharge and re-release that were 1.8 folds that of a commercial RMGI. CLINICAL SIGNIFICANCE: Novel rechargeable nCaF2 orthodontic cement is promising to provide the needed long-term and high levels of F ion releases to inhibit WSLs in orthodontics.

Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles.

Incorporation of proteins into dextran sulfate (DS)-chitosan (CS) nanoparticles (DSCS NPs) is commonly performed using entrapment procedures, in which protein molecules are mixed with DS and CS until particle formation occurs. As DS is an analog of heparin, the authors examined whether proteins could be directly incorporated into preformed DSCS NPs through a heparin binding domain-mediated interaction. The authors formulated negatively-charged DSCS NPs, and quantified the amount of charged DS in the outer shell of the particles. The authors then mixed the DSCS NPs with heparin-binding proteins (SDF-1α, VEGF, FGF-2, BMP-2, or lysozyme) to achieve incorporation. Data show that for DSCS NPs containing 100 nmol charged glucose sulfate units in DS, up to ~1.5 nmol of monomeric or ~0.75 nmol of dimeric heparin-binding proteins were incorporated without significantly altering the size or zeta potential of the particles. Incorporation efficiencies of these proteins were 95%-100%. In contrast, serum albumin or serum globulin showed minimal incorporation (8% and 4%, respectively) in 50% physiological saline, despite their large adsorption in water (80% and 92%, respectively). The NP-incorporated SDF-1α and VEGF exhibited full activity and sustained thermal stability. An in vivo aerosolization study showed that NP-incorporated SDF-1α persisted in rat lungs for 72 h (~34% remaining), while free SDF-1α was no longer detectable after 16 h. As many growth factors and cytokines contain heparin-binding sites/domains, incorporation into preformed DSCS NPs could facilitate in vivo applications of these proteins.

Efficacy of "thick" acellular human dermis (AlloDerm) for lower eyelid reconstruction: comparison with hard palate and thin AlloDerm grafts.

OBJECTIVES: To evaluate the efficacy of thick acellular human dermis (thick AlloDerm [LifeCell Corporation, The Woodlands, Tex]) grafts for posterior and middle lamellae reconstruction to correct lower eyelid retraction and to compare the long-term efficacy of thick AlloDerm with thin AlloDerm and hard palate grafts. METHODS: Retrospective analysis of patients undergoing lower eyelid reconstruction, which encompassed subperiosteal midface lifting, middle lamellae scar lysis, and placement of lower eyelid thick AlloDerm graft. Analysis included 21 surgical procedures in 11 patients. All patients had undergone at least 1 previous lower eyelid surgery with resultant lower eyelid retraction and scleral show. Preoperative and postoperative photographs were used for analysis. Measurements of the corneal diameter and distance from pupil center to lower eyelid margin were obtained, standardized, and compared. RESULTS: Of 21 procedures, 16 (8 of 11 patients) demonstrated improvement of lower eyelid position. The mean improvement of the median marginal reflex distance was 1.6 mm (range, 0.4-2.2 mm). The average follow-up after surgery was 215 days (range, 3-12 months). Of 21 procedures (3 patients), 5 failed to demonstrate improvement of lower eyelid position, with the mean final eyelid position lower postoperatively by 0.8 mm (range, 0.4-1.4 mm). CONCLUSIONS: We demonstrated long-lasting improvement of lower eyelid position with placement of thick AlloDerm grafts during lower eyelid reconstruction. The patients in our study had undergone previous lower eyelid blepharoplasty with resultant middle lamellae tethering. Surgical correction included subperiosteal midface-lift and middle lamellae scar lysis, in addition to thick AlloDerm graft placement to the lower eyelid. The results are comparable to hard palate grafts but perhaps superior to thin AlloDerm grafts.

Preparation and characterization of SDF-1α-chitosan-dextran sulfate nanoparticles.

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under appropriate conditions. The glycan nanoparticles are useful carriers for protein factors, which facilitate the in vivo delivery of the proteins and sustain their retention in the targeted tissue. The glycan polyelectrolyte complexes are also ideal for protein delivery, as the incorporation is carried out in aqueous solution, which reduces the likelihood of inactivation of the proteins. Proteins with a heparin-binding site adhere to dextran sulfate readily, and are, in turn, stabilized by the binding. These particles are also less inflammatory and toxic when delivered in vivo. In the protocol described below, SDF-1α (Stromal cell-derived factor-1α), a stem cell homing factor, is first mixed and incubated with dextran sulfate. Chitosan is added to the mixture to form polyelectrolyte complexes, followed by zinc sulfate to stabilize the complexes with zinc bridges. The resultant SDF-1α-DS-CS particles are measured for size (diameter) and surface charge (zeta potential). The amount of the incorporated SDF-1α is determined, followed by measurements of its in vitro release rate and its chemotactic activity in a particle-bound form.

Postoperative infection with group A beta-hemolytic Streptococcus after blepharoplasty.

PURPOSE: To report a case of group A beta-hemolytic streptococcal infection with signs of early necrotizing fasciitis after cosmetic blepharoplasty in a healthy patient. DESIGN: Interventional case report. METHODS: A healthy 59-year-old woman underwent outpatient bilateral upper and lower blepharoplasty with midface lifting. Thirty hours postoperatively she developed marked pain and edema of the left eyelids and face, and a violaceous eyelid bulla, which heralded early necrotizing fasciitis. Culture of the serosanguinous exudates from the left eyelid revealed group A beta-hemolytic Streptococcus organisms. RESULTS: The patient was treated with intravenous antibiotics, intravenous corticosteroids, hyperbaric oxygen therapy, and wound debridement. The infection resolved with mild cicatrization of the left upper eyelid. CONCLUSIONS: Group A beta-hemolytic Streptococcus is an increasingly recognized cause of infection that occurs after trauma or surgery, even in highly vascularized areas such as the eyelids and face. It is a potentially devastating infection, particularly in vascularly compromised patients, and requires immediate and aggressive treatment.