3D assessment of alveolar bone alterations in orthodontic movement among Indians.

Apical root resorption, which is characterised as a biological or abnormal phenomenon that shortens the length of the root apex, is additional typical iatrogenic impact of orthodontic tooth movement that may jeopardise the effectiveness of treatment and tooth lifespan. The main goals of the current retrospective investigation were to assess the dimensions of alveolar bone alterations that come along with orthodontic movement and to look into the frequency and extent of resorption of root in maxillary incisors across categories that were similarly managed with clear aligners (OCA) and fixed appliances (OFA) using CBCT. The study included 50 subjects who were divided into two categories with 25 study subjects in each category. Category OFA: Subjects receiving OFA (n=25). A CBCT scan was used to get three-dimensional pictures at the beginning of therapy as well as at the end of therapy. The overall resorption of root at apical region in OFA group was 0.63±0.21 mm. The overall resorption of root at apical region in OCA group was 0.32 ±0.36 mm. The difference in observation was statistically significant (p= 0.000) with reduced resorption of root at apical region in clear aligners. It was concluded that the decrease in thickness of alveolar bone was greater in orthodontic fixed appliances group as compared to clear aligners. The resorption of root at apical region was lesser in clear aligners group as compared to fixed appliances.

Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.

Apolipoprotein B (apoB)-lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the interaction between apoB and microsomal triglyceride transfer protein (MTP) in hepatocytes, thereby reducing very-low-density lipoprotein (VLDL) assembly and plasma apoB-lipoprotein cholesterol levels. Plasminogen activator inhibitor 1 (PAI-1) sequesters tPA away from apoB and increases VLDL assembly. Humans with PAI-1 deficiency have smaller VLDL particles and lower plasma levels of apoB-lipoprotein cholesterol. These results suggest a mechanism that fine-tunes VLDL assembly by intracellular interactions among tPA, PAI-1, and apoB in hepatocytes.

Efficacy of Two Types of Noninvasive Nerve Stimulation in the Management of Myofascial Pain Caused by Temporomandibular Joint (TMJ) Disorders.

Background A range of diseases affecting the jaw muscles and/or temporomandibular joint are referred to as temporomandibular disorders (TMDs). Nearly 80% of the general population is affected by TMDs, and 48% of those people have trouble opening their mouths and have painful muscles. Aim To compare the effectiveness of transcutaneous electrical nerve stimulation (TENS) and microcurrent nerve stimulation (MENS) for the relief of masticatory muscle discomfort. Methods Groups I and II were further separated into two groups of 30 persons each (A and B), as well as subgroups C and D. Subjects in Group I received TENS treatment for 20 minutes at frequencies of 0-5 and 5-5 for subgroups A and B, and with visual analog scale (VAS) scores of 1-5 and 6-10 for subgroups C and D, respectively. Subjects in Group II received MENS for 20 minutes, with subgroups C and D receiving the same frequency and VAS score as subgroups A and B, respectively. All individuals underwent treatment with a comparable frequency and length of time every day for five days. Results For subgroup D treated with MENS, there was a considerable reduction in pain; however, for subgroups A and C, there was a comparable reduction in the VAS score for both groups treated with MENS and TENS therapy. Conclusion Compared to TENS, MENS provides quicker and more effective pain relief. Paresthesia and tingling are two adverse effects of TENS that are not present with MENS. However, MENS and TENS are equally helpful at treating masticatory muscle discomfort that is both acute and chronic, as well as improving mouth opening.

Quantifying the Release of Titanium From the Titanium Dioxide-Impregnated Composites Used in Orthodontic Bonding.

BACKGROUND: Previous literature data has extensively assessed the biocompatibility of various orthodontic adhesives and their components, where the results of most of the studies showed cytotoxic effects of different degrees owing to the unbound molecules released structurally from the cured components. AIM: The present in-vitro study was aimed to assess the release of titanium dioxide nanoparticles in the artificial saliva from the orthodontic composites impregnated with titanium dioxide nanoparticles of 5% w/w (weight/weight) and 1% w/w used for metal brackets bonding. METHODS: The study assessed 160 teeth extracted freshly during orthodontic treatment and divided into two groups of 80 samples, each that bonded to orthodontic brackets having 5% w/w and 1% w/w composites with titanium dioxide nanoparticles kept in the artificial saliva. Quantification was done for 5% w/w and 1% w/w composites having titanium nanoparticles with inductively coupled plasma mass spectroscopy at 24 hours, two, four, and six months. RESULTS: It was seen that in teeth with 1% titanium dioxide, the greatest titanium release was seen at two months, with non-significant release after two months. In teeth with 5% w/w titanium dioxide nanoparticles showed significant titanium release all the time. A significantly greater titanium dioxide release on increasing concentration from 1% to 5% was seen for the 5% w/w group at all the assessment times. CONCLUSION: The present study concludes that a higher release of titanium is seen in 5% w/w composite containing titanium dioxide nanoparticles, and the concentrations of 1% and 5% can be safely used and are considered to be within permissible limits.

High Serum Ferritin Levels among Blood Transfused Thalassemic Patients Admitted to the Department of Paediatrics in a Tertiary Care Centre: A Descriptive Cross-Sectional Study.

Introduction: Raised serum ferritin levels often indicate iron overload, but they are not specific as the levels are elevated in inflammatory disorders, liver diseases, alcohol excess, or malignancy. If regular transfusions are required for the patient with thalassemia, this doubles the rate of iron accumulation leading to earlier massive iron overload and iron-related damage. The aim of this study aimed to find out the prevalence of high serum ferritin levels among blood-transfused thalassemic patients admitted to the Department of Paediatrics in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted at a tertiary care centre from 1 March 2022 to 31 December 2022. Ethical approval was taken from the Institutional Review Committee (Reference number: 078/79-017/HG). Children who were confirmed by haemoglobin electrophoresis on regular blood transfusion were included in the study. Those who did not gave consent were excluded from the study. Convenience sampling method was used. Point estimate and 90% Confidence Interval were calculated. Results: Out of 53 cases, the prevalence of high serum ferritin level was seen in 46 (88.79%) (80.30-97.28, 95% Confidence Interval). Among 46, 34 (73.91%) had serum ferritin levels of more than 1000 to 2500 ng/ml whereas 12 (26.09%) had more than 25000 ng/ml. Conclusions: The prevalence of high serum ferritin levels among blood transfused thalassemic patients admitted to the Department of Paediatrics in a tertiary care centre was found to be higher than in other studies done in similar settings. Keywords: blood transfusion; ferritin; thalassemia.

Foldscope: Diagnostic Accuracy and Feasibility of its Use in National Malaria Control Program.

Background: Malaria has been an important public health all over the globe. Although conventional light microscopy is the gold standard of diagnosis, light microscopes are heavy, fragile, costly, and electricity dependent. Rapid diagnostic tests (RDTs) have become more popular but perform badly in temperate climate. This is because the RDT kits require maintenance of cold chain for its optimal use. In this regard, there is a recent interest in handheld malaria microscopy at the point of care in the field setting. Foldscopes are cheap, handy, nonfragile, and use mobile camera for illumination. The purpose of the study was to find whether foldscope can be used in the national vector borne disease control program (NVBDCP) in India. Methods: Ten laboratory technicians were trained in identifying malaria parasites using foldscope and their mobiles. Later, they were provided with unassembled foldscope to document their test results for the preidentified malaria slides. The blood smears were stained as per the protocol of NVBDCP. The report of the index test (foldscope microscopy) was compared with the reference test (conventional microscopy). Results: The sensitivity and specificity of the index test was found to be 13.3% (6.257-26.18), specificity of 97.78% (88.43-99.61), positive predictive value 85.71% (48.69-97.43), and negative predictive value 53.01% (42.38-63.38). The devise failure rate and test failure rate were 20% and 11.7%. The kappa agreement between the index and reference microscopy was only 11% and the McNemar P < 0.01. Conclusion: The ×400 foldscope at its present magnification and illumination cannot be utilized in the field under NVBDCP.

Evaluation of Immature Granulocyte Count as the Earliest Biomarker for Sepsis.

Background: Diagnosing sepsis early is important for its successful management. Various biomarkers are being used currently, but mostly they are either expensive or not readily available. This study aims to evaluate usefulness of automated immature granulocyte count (IG#) and immature granulocyte percentage (IG%) as early diagnostic markers of sepsis and compares it to other established predictive markers. Patients and methods: In this prospective observational study, 137 eligible, critically ill, nonseptic intensive care unit patients were analyzed for automated IG#, IG%, serum procalcitonin (PCT), and blood lactate (Lac), daily for 7 days after recruitment. Patients were followed for the development of sepsis, defined by the new Sepsis-3 criteria. The study was divided into four time periods of 24 hours each with respect to the day of developing organ dysfunction. Using area under receiver operator characteristic and diagnostic odds ratio (DOR) methods, the best biomarker for the prediction of sepsis in each time period was calculated. Results: IG# and IG% were the earliest biomarkers to have a significant discriminating value with area under the curve of 0.81 and 0.82, respectively, as early as 24 hours before clinical sepsis is diagnosed by Sepsis-3 criteria. Both IG# and IG% have a high DOR of 34.91 and 18.11, respectively, when compared to others like PCT and Lac having a DOR of 27.06 and 4.78, respectively. Conclusion: IG# and IG% are easily available, rapid, and inexpensive tools to differentiate between septic and nonseptic patients with high specificity and sensitivity. It is the earliest biomarker to show a significant rise in patients developing sepsis. How to cite this article: Bhansaly P, Mehta S, Sharma N, Gupta E, Mehta S, Gupta S. Evaluation of Immature Granulocyte Count as the Earliest Biomarker for Sepsis. Indian J Crit Care Med 2022;26(2):216-223.

Zika Virus Prediction Using AI-Driven Technology and Hybrid Optimization Algorithm in Healthcare.

The Zika virus presents an extraordinary public health hazard after spreading from Brazil to the Americas. In the absence of credible forecasts of the outbreak's geographic scope and infection frequency, international public health agencies were unable to plan and allocate surveillance resources efficiently. An RNA test will be done on the subjects if they are found to be infected with Zika virus. By training the specified characteristics, the suggested Hybrid Optimization Algorithm such as multilayer perceptron with probabilistic optimization strategy gives forth a greater accuracy rate. The MATLAB program incorporates numerous machine learning algorithms and artificial intelligence methodologies. It reduces forecast time while retaining excellent accuracy. The projected classes are encrypted and sent to patients. The Advanced Encryption Standard (AES) and TRIPLE Data Encryption Standard (TEDS) are combined to make this possible (DES). The experimental outcomes improve the accuracy of patient results communication. Cryptosystem processing acquires minimal timing of 0.15 s with 91.25 percent accuracy.

Factor V east Texas variant causes bleeding in a three-generation family.

BACKGROUND: The factor V east Texas bleeding disorder (FVETBD) is caused by increased plasma tissue factor pathway inhibitor-α (TFPIα) concentration. The underlying cause is a variant in F5 causing alternative splicing within exon 13 and producing FV-short, which tightly binds the C-terminus of TFPIα, prolonging its circulatory half-life. OBJECTIVES: To diagnose a family presenting with variable bleeding and laboratory phenotypes. PATIENTS/METHODS: Samples were obtained from 17 family members for F5 exon 13 sequencing. Plasma/platelet TFPI and platelet FV were measured by ELISA and/or western blot. Plasma thrombin generation potential was evaluated using calibrated automated thrombography. RESULTS: The FVET variant was identified in all family members with bleeding symptoms and associated with elevated plasma TFPIα (4.5- to 13.4-fold) and total TFPI (2- to 3-fold). However, TFPIα and FV-short were not elevated in platelets. TF-initiated thrombin generation in patient plasma was diminished but was restored by a monoclonal anti-TFPI antibody or factor VIIa. TFPIα localized within vascular extracellular matrix in an oral lesion biopsy from an affected family member. CONCLUSIONS: Factor V east Texas bleeding disorder was diagnosed in an extended family. The variant was autosomal dominant and highly penetrant. Elevated plasma TFPIα, rather than platelet TFPIα, was likely the primary cause of bleeding. Plasma FV-short did not deplete TFPIα from extracellular matrix. In vitro thrombin generation was restored with an anti-TFPI antibody or factor VIIa suggesting effective therapies may be available. Increased awareness of, and testing for, bleeding disorders associated with F5 exon 13 variants and elevated plasma TFPI are needed.

Short Ejaculatory Abstinence in Normozoospermic Men is Associated with Higher Clinical Pregnancy Rates in Sub-fertile Couples Undergoing Intra-Cytoplasmic Sperm Injection in Assisted Reproductive Technology: A Retrospective Analysis of 1691 Cycles.

BACKGROUND: The current WHO abstinence recommendations are ideal only for clinical diagnosis, as in recent years a negative correlation of abstinence duration with good embryo development and clinical pregnancy rate has been seen. AIM: The aim of the study was to evaluate the impact of variation in abstinence period on fertilization, embryo development potential, pregnancy, and miscarriage rate in sub-fertile couples undergoing assisted reproductive technology (ART) treatment. SETTING AND DESIGN: A prospective analysis was conducted at a tertiary (level 3) infertility care clinic. MATERIALS AND METHODS: The study included analysis of 1691 cycles for the patient undergoing ART procedures between September 2017 and August 2019. The influence of ejaculatory abstinence (EA) was investigated based on variation in abstinence length with four groups: Group I - 1 day; Group II - 2-5 days; Group III - 6-7 days; and Group IV - EA length of ≥8 days. STATISTICAL ANALYSIS: Analysis of variance and Chi-square test were used to calculate P value. RESULTS: In our primary outcome, we have seen a strong positive correlation of abstinence duration with semen volume, total sperm count, total motile count, and difference between each group was significant. Secondary outcomes showed a significantly higher implantation rate, biochemical pregnancy rate was observed in Group I (1 day) per embryo transfer as compared to longer abstinence groups. This resulted in significantly higher clinical pregnancy rates in Group I 30.0% vs. 25.4% in comparison to longer abstinence groups. CONCLUSIONS: Our study has shown duration of abstinence is negatively correlated with positive ß-human chorionic gonadotropin rate, clinical pregnancy rate, and implantation rate. Lower miscarriage rate was also observed with shorter abstinence duration.

Identification of Cardiac Fibrosis in Young Adults With a Homozygous Frameshift Variant in SERPINE1.

Importance: Cardiac fibrosis is exceedingly rare in young adults. Identification of genetic variants that cause early-onset cardiomyopathy may inform novel biological pathways. Experimental models and a single case report have linked genetic deficiency of plasminogen activator inhibitor-1 (PAI-1), a downstream target of cardiac transforming growth factor ß, with cardiac fibrosis. Objective: To perform detailed cardiovascular phenotyping and genotyping in young adults from an Amish family with a frameshift variant (c.699_700dupTA) in SERPINE1, the gene that codes for PAI-1. Design, Setting, and Participants: This observational study included participants from 3 related nuclear families from an Amish community in the primary analysis and participants from the extended family in the secondary analysis. Participants were recruited from May 2015 to December 2016, and analysis took place from June 2015 to June 2020. Main Outcomes and Measures: (1) Multimodality cardiovascular imaging (transthoracic echocardiography and cardiac magnetic resonance imaging), (2) whole-exome sequencing, and (3) induced pluripotent stem cell-derived cardiomyocytes. Results: Among 17 participants included in the primary analysis, the mean (interquartile range) age was 23.7 (20.9-29.9) years and 9 individuals (52.9%) were confirmed to be homozygous for the SERPINE1 c.699_700dupTA variant. Late gadolinium enhancement was present in 6 of 9 homozygous participants (67%) with absolute PAI-1 deficiency vs 0 of 8 in the control group (P = .001). Late gadolinium enhancement patterns tended to be dense and linear, usually subepicardial but also midmyocardial and transmural with noncoronary distributions. Targeted whole-exome sequencing analysis identified that homozygosity for c.699_700dupTA SERPINE1 was the only shared pathogenic variant or variant of uncertain significance after examination of cardiomyopathy genes among those with late gadolinium enhancement. Induced pluripotent stem cell-derived cardiomyocytes from participants homozygous for the SERPINE1 c.699_700dupTA variant exhibited susceptibility to cardiomyocyte injury in response to angiotensin II (increased transforming growth factor ß1 secretion and release of lactate dehydrogenase) compared with control induced pluripotent stem cell-derived cardiomyocytes. In a secondary analysis based on echocardiography in 155 individuals across 3 generations in the extended family, no difference in global longitudinal strain was observed in carriers for the SERPINE1 c.699_700dupTA variant compared with wild-type participants, supporting an autosomal recessive inheritance pattern. Conclusions and Relevance: In this study, a highly penetrant, autosomal recessive, cardiac fibrosis phenotype among young adults with homozygous frameshift variant for SERPINE1 was identified, suggesting an optimal range of PAI-1 levels are needed for cardiac homeostasis.

lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation.

Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation. BRD3 binds to histone H3 acetylated at lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and the depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings show that cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest that protein-lncRNA phase-separated condensates have a broader role as regulators of transcription.

Laboratory misdiagnosis of von Willebrand disease in post-menarchal females: A multi-center study.

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off-site laboratory processing, instead of a coagulation facility with onsite processing. Off-site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off-site and onsite specimen processing for VWD in this multicenter, retrospective study. We enrolled females aged 12 to 50 years who had off-site specimen processing for VWF assays, and repeat testing performed at a consulting institution with onsite coagulation phlebotomy and processing. A total of 263 females from 17 institutions were included in the analysis. There were 251 subjects with both off-site and onsite VWF antigen (VWF:Ag) processing with 96 (38%) being low off-site and 56 (22%) low onsite; 223 subjects had VWF ristocetin co-factor (VWF:RCo), 122 (55%) were low off-site and 71 (32%) were low onsite. Similarly, 229 subjects had a Factor VIII (FVIII) assay, and 67 (29%) were low off-site with less than half, 29 (13%) confirmed low with onsite processing. Higher proportions of patients demonstrated low VWF:Ag, VWF:RCo, and/or FVIII with off-site processing compared to onsite (McNemar's test P-value <.0005, for all assays). These results emphasize the need to decrease delays from sample procurement to processing for VWF assays. The VWF assays should ideally be collected and processed at the same site under the guidance of a hematologist.

A Preliminary Experience of Integration of an Electronic Witness System, its Validation, Efficacy on Lab Performance, and Staff Satisfaction Assessment in a Busy Indian in vitro Fertilization Laboratory.

BACKGROUND: Electronic witness system (EWS) is one of the recent advancements in the field of in vitro fertilization (IVF) that uses radiofrequency identification (RFID) technology to monitor all critical work carried out in each stage of IVF procedures cycle. OBJECTIVE: The main objective of the study was validation and integration of electronic witnessing system, assessment of its efficacy on lab performance, and staff satisfaction in a busy tertiary IVF center. MATERIALS AND METHODS: The study data included analysis of 187 consecutive cycles for installation and validation of EWS. The laboratory outcomes were analyzed for development of good-quality embryos followed up for the pregnancy outcome. RESULTS: A total of 751 RFIG tags were involved with 77 patient-assigned barcodes for the all the analyzed cycles. During validation of EWS, a total of 02 (0.46%) red flags were highlighted by EWS from pre-allocated tags within the frequency range of the reader. The maturation rate (83.1%), fertilization rate (74.3%), cleavage rate (93.5%), day 3 grade-A embryo development rate (64.6%), good grade blastocyst development rate (26.4%) were observed in EWS group that was comparable to other groups with no significant difference (P > 0.005). Frozen embryo transfer of EWS cases observed a clinical pregnancy rate (50.0%) that was higher than other groups though statistically not significant as sample size was small. CONCLUSIONS: Our preliminary study suggests that EWS does not affect the gametes, embryos, and pregnancy rate, however a larger randomized clinical trials should be undertaken to evaluate the safety and efficacy of EWS.

Potential of the Community Counts registry to characterize rare bleeding disorders.

INTRODUCTION: Rare bleeding disorders (RBDs) comprise of heterogeneous coagulation factor deficiencies and platelet disorders that are underreported worldwide. AIM: First report on RBD data from United States haemophilia treatment center network (USHTCN). METHODS: A national surveillance system for the federally recognized USHTCN developed in collaboration with the Centers for Disease Control and Prevention (CDC) and American Thrombosis and Haemostasis Network (ATHN) was queried for patients with RBDs. Patient counts were extracted from the HTC Population Profile (HTC PP) component including limited data on patients followed through the USHTCN, and from the Registry component, including patient authorized, detailed clinical data. The prevalence of RBDs in the United States was estimated based on the HTC PP data and compared to the expected national prevalence based on data extrapolated from Orphanet, an international registry. RESULTS: Based on the estimated prevalence of RBD in the overall 2017 US population, the cases in the HTC network were lower than expected for FI, FII, FX, and FV + FVIII deficiencies by 36%, 61%, 75% and 94%, respectively, and higher than expected for FXIII, FV, FVII, and FXI deficiencies by 7%, 14%, 33% and 185%, respectively. The proportion of RBD patients reported in the HTC PP, enrolled in the Registry, was 10.8%. CONCLUSIONS: There is a clear need to identify individuals with RBDs who could benefit from the comprehensive care provided in the USHTCN. In addition, increased enrolment of people with all RBDs in the Registry is needed to improve knowledge of treatment outcomes of patients with RBDs in the United States.

Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency.

INTRODUCTION: Deficiencies of plasminogen and plasminogen activator inhibitor type 1 (PAI-1) are rare disorders of fibrinolysis. Current laboratory assays for analysis of activity of plasminogen and PAI-1 do not provide an accurate correlation with clinical phenotype. METHODS: The Nijmegen Hemostasis Assay (NHA) was used to simultaneously measure thrombin and plasmin generation in 5 patients with plasminogen deficiency (PLGD) and 10 patients with complete PAI-1 deficiency. Parameters analysed included: lag time ratio, thrombin peak time ratio, thrombin peak height, thrombin potential (AUC), fibrin lysis time, plasmin peak height and plasmin potential. Parameters were expressed as a percentage compared to a reference value of 53 healthy normal controls. RESULTS: Patients with PLGD demonstrated a short lag time and thrombin peak time, with normal thrombin peak height but an increased AUC. Plasmin generation was able to be detected in only one (23% plasminogen activity) of the five PLGD patients. All ten PAI-1 deficient patients demonstrated a short lag and thrombin peak time, low thrombin peak height with normal AUC. Plasmin generation revealed an increased plasmin peak and plasmin potential; interestingly, there was a large variation between individual patients despite all patients having the same homozygous defect. CONCLUSION: Patients with either PLGD or PAI-1 deficiency show distinct abnormalities in plasmin and thrombin generation in the NHA. The differences observed in the propagation phase of thrombin generation may be explained by plasmin generation. These results suggest that disorders of fibrinolysis also influence coagulation and a global assay measuring both activities may better correlate with clinical outcome.

Sustained release of a model water-soluble compound via dry powder aerosolizable acetalated dextran microparticles.

Objective: To design and characterize aerosol microparticles (MP) to provide sustained release of the water-soluble compound sulforhodamine B (SRB) and achieve effective aerosol dispersion. Significance: Modulating the release of water-soluble compounds remains a challenge in pulmonary drug delivery. Methods: SRB and water made up an aqueous solution, while acetalated dextran (Ac-Dex) and isopropyl alcohol made up an organic solution. The two solutions were mixed together, and the solution was spray dried to produce MP. MP were characterized for morphology, size, release kinetics, aerosol dispersion, and cellular interactions. Results: Ac-Dex MP exhibited corrugated morphology and aerodynamic diameters from 2.06 to 2.86 µm. MP deposited in all stages of a Next Generation Impactor, with >90% fine particle fraction. MP exhibited encapsulation efficiencies >129% with SRB loading values up to 16.7 µg SRB/mg MP. MP exhibited sustained release of SRB at pH 7 and fast release at pH 5. In vitro experiments showed minimal cytotoxicity, successful uptake of MP in epithelial cells, and no disruption to the integrity of epithelial monolayers. Conclusions: Ac-Dex MP systems demonstrated the ability to provide sustained the release of a water-soluble therapeutic in addition to effective aerosol dispersion for pulmonary applications.

Clinical features of children, adolescents, and adults with coexisting hypermobility syndromes and von Willebrand disease.

We present five patients with coexistent von Willebrand disease (VWD) and Ehlers-Danlos syndrome and 21 with VWD and joint hypermobility. Females outnumbered males ten to three, Beighton scores were documented in 58% (15 of 26 patients), and several patients experienced moderately severe bleeding. We believe coexistent hypermobility disorder with VWD potentially affects bleeding severity and want to raise awareness among hematologists. Evaluation by geneticists is recommended because of the varying complexities observed across the disease spectrum, and the availability of new genetic tests should lead to more accurate diagnoses for the various hypermobility disorders.

Erratum to: Decellularization Methods for Scaffold Fabrication.

The publisher regrets that an author was not mentioned in the chapter by mistake. The details of the author are provided below:Archna Dhasmana - Department of Polymer and Process Engineering, Indian Institute of Technology, Roorkee, India.