Reply to Singh, G.D. Comment on "Dao et al. Retrospective Analysis of Real-World Data for the Treatment of Obstructive Sleep Apnea with Slow Maxillary Expansion Using a Unique Expansion Dental Appliance (DNA). Pathophysiology 2023, 30, 199-208".

In response to the commentary "Response to 'Retrospective analysis of real-world data for the treatment of obstructive sleep apnea with slow maxillary expansion'" [...].

Retrospective Analysis of Real-World Data for the Treatment of Obstructive Sleep Apnea with Slow Maxillary Expansion Using a Unique Expansion Dental Appliance (DNA).

In addition to mandibular advancement devices, dental expansion appliances are an important clinical approach for achieving an increased intra-oral space that promotes airflow and lessens the frequency or severity of apneic events in patients diagnosed with obstructive sleep apnea (OSA). It has been thought that dental expansion in adults must be preceded by oral surgery; however, in this paper, we examine the results of a new technique for slow maxillary expansion without any surgical procedures. The palatal expansion device, DNA (Daytime-Nighttime Appliance), was reviewed in this retrospective study, particularly regarding its effects on measurements of transpalatal width, airway volume, and apnea-hypopnea indices (AHI) as well as its common modalities and complications. The DNA effectively reduced AHI by 46% (p = 0.00001) and significantly increased both airway volume and transpalatal width (p < 0.00001). After DNA treatment, 80% of patients showed some improvement in AHI scores with 28% of patients having their OSA symptoms completely resolved. Compared to the use of mandibular appliances, this approach is intended to create a sustained improvement in airway management that can reduce or eliminate dependence on continuous positive airway pressure (CPAP) or other OSA treatment devices.

Applications of acellular human amniotic membrane in regenerative medicine.

The human amniotic membrane (hAM) surrounds and protects the fetus. It mainly consists of a thick basement membrane and an avascular stromal matrix. The structural, physical, and biological properties of AM make it a wonderful choice to use in regenerative medicine applications. This review discusses recent applications of hAM in skin transplantation and wound healing, ophthalmology, orthopedics, cell culture matrix, cell delivery system, cardiac injury, male and female reproductive systems, and liver. Moreover, an overview is presented on the advantages and disadvantages of using hAM and some methods to systematically refine and standardize hAM preparation.

Dysregulated Sulfide Metabolism in Multiple Sclerosis: Serum and Vascular Endothelial Inflammatory Responses.

Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. When diagnosed early, MS can be managed more effectively, stabilizing clinical symptoms and delaying disease progression. The identification of specific serum biomarkers for early-stage MS could facilitate more successful treatment of this condition. Because MS is an inflammatory disease, we assessed changes in enzymes of the endothelial hydrogen sulfide (H2S) pathway in response to inflammatory cytokines. Blotting analysis was conducted to detect Cystathionine γ-lyase (CSE), Cystathionine beta synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST) in human brain microvascular endothelial apical and basolateral microparticles (MPs) and cells following exposure to tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). CSE was increased in MPs and cells by exposure to TNF-α/IFN-γ; CBS was elevated in apical MPs but not in cells or basolateral MPs; MST was not significantly affected by cytokine exposure. To test how our findings relate to MS patients, we evaluated levels of CSE, CBS, and MST in serum samples from healthy control and MS patients. We found significantly decreased levels of CBS and MST (p = 0.0004, 0.009) in MS serum samples, whereas serum levels of CSE were marginally increased (p = 0.06). These observations support increased CSE and lower CBS and MST expression being associated with the vascular inflammation in MS. These changes in endothelial-derived sulfide enzymes at sites of inflammation in the brain may help to explain sulfide-dependent changes in vascular dysfunction/neuroinflammation underlying MS. These findings further support the use of serum samples to assess enzymatic biomarkers derived from circulating MPs. For example, "liquid biopsy" can be an important tool for allowing early diagnosis of MS, prior to the advanced progression of neurodegeneration associated with this disease.

SLAMF1 is expressed and secreted by hepatocytes and the liver in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver disease in the United States and worldwide. Nonalcoholic steatohepatitis (NASH), the most advanced form of NAFLD, is characterized by hepatic steatosis associated with inflammation and hepatocyte death. No treatments are currently available for NASH other than lifestyle changes, and the disease lacks specific biomarkers. The signaling lymphocytic activation molecule family 1 (SLAMF1) protein is a self-ligand receptor that plays a role in orchestrating an immune response to some pathogens and cancers. We found that livers from humans and mice with NASH showed a more prominent immunohistochemistry staining for SLAMF1 than non-NASH controls. Furthermore, SLAMF1 levels are significantly increased in NASH plasma samples from mice and humans compared with their respective controls. In mice, the levels of SLAMF1 correlated significantly with the severity of the NASH phenotype. To test whether SLAMF 1 is expressed by hepatocytes, HepG2 cells and primary murine hepatocytes were treated with palmitic acid (PA) to induce a state of lipotoxicity mimicking NASH. We found that PA treatments of HepG2 cells and primary hepatocytes lead to significant increases in SLAMF1 levels. The downregulation of SLAMF1 in HepG2 cells improved the cell viability and reduced cytotoxicity. The in vivo data using mouse and human NASH samples suggests a potential role for this protein as a noninvasive biomarker for NASH. The in vitro data suggest a role for SLAMF1 as a potential therapeutic target to prevent hepatocyte death in response to lipotoxicity.NEW & NOTEWORTHY This study identified for the first time SLAMF1 as a mediator of hepatocyte death in nonalcoholic fatty liver disease (NASH) and as a marker of NASH in humans. There are no pharmacological treatments available for NASH, and diagnostic tools are limited to invasive liver biopsies. Therefore, since SLAMF1 levels correlate with disease progression and SLAMF1 mediates cytotoxic effects, this protein can be used as a therapeutic target and a clinical biomarker of NASH.

An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma.

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered.

The Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy.

Ischemic stroke remains the leading cause of neurologically based morbidity and mortality. Current stroke treatment is limited to two classes of FDA-approved drugs: thrombolytic agents (tissue plasminogen activator (tPA)) and antithrombotic agents (aspirin and heparin), which have a narrow time-window (<4.5 h) for administration after onset of stroke symptoms. While thrombolytic agents restore perfusion, they carry serious risks for hemorrhage, and do not influence damage responses during reperfusion. Consequently, stroke therapies that can suppress deleterious effects of ischemic injury are desperately needed. Angiotensin converting enzyme-2 (ACE2) has been recently suggested to beneficially influence experimental stroke outcomes by converting the vasoconstrictor Ang II into the vasodilator Ang 1-7. In this review, we extensively discuss the protective functions of ACE2-Ang (1-7)-MasR axis of renin angiotensin system (RAS) in ischemic stroke.

Human placenta mesenchymal stem cell protection in ischemic stroke is angiotensin converting enzyme-2 and masR receptor-dependent.

Thromboembolic stroke remains a major cause of neurological disability and death. Current stroke treatments (aspirin, tissue plasminogen activator) are significantly limited by timing and risks for hemorrhage which have driven researchers to explore other approaches. Stem cell-based therapy appears to be an effective option for ischemic stroke. Besides trans-differentiation into neural cells, stem cells also provide acute protection via paracrine signaling pathways through which releasing neuroprotective factors. We previously reported that intraperitoneal administration of human placenta mesenchymal stem cell (hPMSC) therapy upon reperfusion significantly protected the brain against middle cerebral artery occlusion (MCAO)-induced injury. In the present study, we specifically investigated the role of hPMSC-derived angiotensin converting enzyme-2 (ACE-2) in protection of MCAO-induced brain injury by measurement of brain tissue viability, cerebral blood flow, and neurological score. Here, we report for the first time that hPMSC expressing substantial amount of ACE-2, which mediates hPMSC protection in the MCAO model. Strikingly, we found that the protective effects of hPMSC in MCAO-induced brain injury could be attenuated by pretreatment of hPMSCs with MLN-4760, a specific inhibitor of ACE-2 activity, or by transfection of hPMSCs with ACE-2-shRNA-lentivirus. The hPMSC-derived ACE-2 specific protective mechanism was further demonstrated by administration of PD123319, an Angiotensin type-2 receptor antagonist, or A779, a MasR antagonist. Importantly, our study demonstrated that the protective effects of hPMSC in experimental stroke are ACE-2/MasR dependent and this signaling pathway represents an innovative and highly promising approach for targeted stroke therapy.

Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.

Human placental mesenchymal stem cells improve stroke outcomes via extracellular vesicles-mediated preservation of cerebral blood flow.

BACKGROUND: Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have yet to be fully defined. METHODS: We evaluated the protection effect of human placenta mesenchymal stem cells (hPMSC) as a potential form of SCT in experimental ischemic stroke 'transient middle cerebral artery occusion (MCAO)/reperfusion' mice model. FINDINGS: We found for the first time that intraperitoneal administration of hPMSCs or intravenous hPMSC-derived EVs, given at the time of reperfusion, significantly protected the ipsilateral hemisphere from ischemic injury. This protection was associated with significant restoration of normal blood flow to the post-MCAO brain. More importantly, EVs derived from hPMSC promote paracrine-based protection of SCT in the MCAO model in a cholesterol/lipid-dependent manner. INTERPRETATION: Together, our results demonstrated beneficial effects of hPMSC/EVs in experimental stroke models which could permit the rapid "translation" of these cells into clinical trials in the near-term.

Nanoparticle-Encapsulated Bryostatin-1 Activates α-Secretase and PKC Isoforms In vitro and Facilitates Acquisition and Retention of Spatial Learning in an Alzheimer's Disease Mouse Model.

BACKGROUND: Alzheimer's disease (AD) animal models have revealed neuroprotective actions of Bryostatin-1 mediated by activation of novel PKC isoforms, suppression of beta-amyloid and downregulation of inflammatory and angiogenic events, making Bryostatin-1 an attractive candidate for attenuating AD-associated neural, vascular, and cognitive disturbances. OBJECTIVE: To further enhance Bryostatin-1 efficacy, nanoparticle-encapsulated Bryostatin-1 formulations were prepared. METHODS: We compared nano-encapsulated and unmodified Bryostatin-1 in in vitro models of neuronal PKC-d, PKC-e isoforms, α-secretase and studied nano-encapsulated Bryostatin-1 in an AD mouse model of spatial memory (BC3-Tg (APPswe, PSEN1 dE9) 85Dbo/J mice). RESULTS: We found that nanoencapsulated Bryostatin-1 formulations displayed activity greater or equal to that of unmodified Bryostatin-1 in PKC-δ and -ε and α-secretase activation assays. We next evaluated how treatment with a nanoencapsulated Bryostatin-1 formulation facilitated spatial learning in the Morris water maze. AD transgenic mice (6.5 to 8 months of age) were treated with nanoparticle encapsulated Bryostatin-1 formulation (1, 2.5, or 5 µg/mouse) three times the week before testing and then daily for each of the 5 days of testing. Across the acquisition phase, mice treated with nanoencapsulated Bryostatin-1 had shorter latencies, increased % time in the target zone and decreased % time in the opposite quadrant. The mice were given retention testing after a 2-week period without drug treatment. Mice treated with nanoencapsulated Bryostatin-1 had shorter latencies to find the escape platform, indicating retention of spatial memory. CONCLUSION: These data suggest that cognitive deficits associated with AD could be treated using highly potent nanoparticle-encapsulated formulations of Bryostatin-1.

Autologous Adipose Tissue-Derived Mesenchymal Stem Cells Introduced by Biliary Stents or Local Immersion in Porcine Bile Duct Anastomoses.

Biliary complications (strictures and leaks) represent major limitations in living donor liver transplantation. Mesenchymal stem cells (MSCs) are a promising modality to prevent biliary complications because of immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose-derived MSC delivery to biliary anastomoses in a porcine model. Secondary objectives were defining the optimal method of delivery (intraluminal versus extraluminal) and to investigate MSC engraftment, angiogenesis, and fibrosis. Pigs were divided into 3 groups. Animals underwent adipose collection, MSC isolation, and expansion. Two weeks later, animals underwent bile duct transection, reanastomosis, and stent insertion. Group 1 received plastic stents wrapped in unseeded Vicryl mesh. Group 2 received stents wrapped in MSC-seeded mesh. Group 3 received unwrapped stents with the anastomosis immersed in an MSC suspension. Animals were killed 1 month after stent insertion when cholangiograms and biliary tissue were obtained. Serum was collected for liver biochemistries. Tissue was used for hematoxylin-eosin and trichrome staining and immunohistochemistry for MSC markers (CD44 and CD34) and for a marker of neoangiogenesis (CD31). There were no intraoperative complications. One pig died on postoperative day 3 due to acute cholangitis. All others recovered without complications. Cholangiography demonstrated no biliary leaks and minimal luminal narrowing. Surviving animals exhibited no symptoms, abnormal liver biochemistries, or clinically significant biliary stricturing. Group 3 showed significantly greater CD44 and CD34 staining, indicating MSC engraftment. Fibrosis was reduced at the anastomotic site in group 3 based on trichrome stain. CD31 staining of group 3 was more pronounced, supporting enhanced neoangiogenesis. In conclusion, adipose-derived MSCs were safely applied to biliary anastomoses. MSCs were locally engrafted within the bile duct and may have beneficial effects in terms of fibrosis and angiogenesis.

Antibiotics in 3D-printed implants, instruments and materials: benefits, challenges and future directions.

3D printing is an additive manufacturing technology, which permits innovative approaches for incorporating antibiotics into 3D printed constructs. Antibiotic-incorporating applications in medicine have included medical implants, prostheses, along with procedural and surgical instruments. 3D-printed antibiotic-impregnated devices offer the advantages of increased surface area for drug distribution, sequential layers of antibiotics produced through layer-by-layer fabrication, and the ability to rapidly fabricate constructs based on patient-specific anatomies. To date, fused deposition modeling has been the main 3D printing method used to incorporate antibiotics, although inkjet and stereolithography techniques have also been described. This review offers a state-of-the-art summary of studies that incorporate antibiotics into 3D-printed constructs and summarizes the rationale, challenges, and future directions for the potential use of this technology in patient care.

Bilateral Vocal Fold Paralysis After Epidural Anesthesia.

Cranial neuropathies are known potential complications of spinal anesthesia, with most reports describing upper cranial nerve involvement. Intrathecal hypotension resulting in traction injury of the cranial nerves is the likely mechanism of injury. Unilateral vagal neuropathy was first described recently. The patient discussed in this case presented with hoarseness and dysphagia after receiving epidural anesthesia for childbirth. Following videostroboscopy and laryngeal electromyogram, she was diagnosed with bilateral vocal fold paralysis. The patient was managed conservatively with expectant management. She exhibited complete spontaneous recovery, as has been the natural history previously described for similar injuries. The proposed mechanism for this patient, and in others described in the literature, is puncture of the dura with subsequent egress of cerebrospinal fluid, leading to intracranial hypotension and traction on cranial nerves. Unilateral vocal fold paralysis following spinal anesthesia has been reported in one case series consisting of three patients, but this represents the first case of bilateral paralysis. Spontaneous resolution has been observed in all patients. Patients presenting with idiopathic vocal fold paralysis, in summary, should be questioned about recent history of epidural or spinal anesthesia, as a positive history may point to transient intrathecal hypotension as a potential etiology of the paralysis.

Debilitating Metastatic Spindle Cell Carcinoma of the Breast.

Spindle cell carcinoma of the breast is a rare malignancy. If diagnosed and treated in a timely manner, it is generally associated with a good prognosis. Herein, we have presented an interesting case of metastatic spindle cell carcinoma of breast origin, with extensive metastasis and an unusually aggressive disease course. We also discussed refractory hypoglycemia as a fatal complication of highly metabolically active malignancy. Lastly, we briefly explored the importance of seeking medical attention for early detection and treatment and the need to address psychosocial barriers that influence breast cancer screening.

3D Printing for Bio-Synthetic Biliary Stents.

Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. The biofabrication method in the present study examined 3D printing and collagen injection molding for rapid prototyping of customized living biliary stents with clinical applications in the setting of malignant and benign bile duct obstructions. XL-PVA stents showed hydrophilic swelling and addition of radiocontrast to the stent matrix improved radiographic opacity. Collagen loaded with PMSCs contracted tightly around hydrophilic stents and dense choloangiocyte coatings were verified through histology and fluorescence microscopy. It is anticipated that design elements used in these stents may enable appropriate stent placement, provide protection of the stent-stem cell matrix against bile constituents, and potentially limit biofilm development. Overall, this approach may allow physicians to create personalized bio-integrating stents for use in biliary procedures and lays a foundation for new patient-specific stent fabrication techniques.

Radioactive Iodine-Refractory Differentiated Thyroid Cancer in the Elderly.

Most common thyroid cancers are differentiated thyroid cancers (DTCs) and have papillary, follicular, or Hürthle cell morphology. Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland. The incidence of DTC increases with age. While most of the patients with DTC have an excellent prognosis, the outcome can be poor when diagnosed in elderly patients. PURPOSE OF REVIEW: Current treatment approach for DTC includes surgery, thyroid-stimulating hormone (TSH) suppression, radioactive iodine, external beam radiotherapy, or systemic treatments such as kinase inhibitors. Radioactive iodine therapy (RAI) is the primary first-line systemic treatment for advanced DTC. However, during the course of treatment, the tumor may become refractory to RAI. Elderly patients are more likely to be diagnosed with advanced disease that can be refractory to RAI. RECENT FINDINGS: The advent of TKIs (tyrosine kinase inhibitors) and their usage in RAI refractory disease has shown improved progression-free survival. These agents are, however, associated with increased toxicity. The variable nature of disease and toxicity associated with the systemic therapy makes it important to have an individualized approach to management, especially in the elderly population who can be more susceptible to toxicities.

Obstructive Lymphangitis Precedes Colitis in Murine Norovirus-Infected Stat1-Deficient Mice.

Murine norovirus (MNV) is an RNA virus that can prove lethal in mice with impaired innate immunity. We found that MNV-4 infection of Stat1-/- mice was not lethal, but produced a 100% penetrant, previously undescribed lymphatic phenotype characterized by chronic-active lymphangitis with hepatitis, splenitis, and chronic cecal and colonic inflammation. Lesion pathogenesis progressed from early ileal enteritis and regional dilated lymphatics to lymphangitis, granulomatous changes in the liver and spleen, and, ultimately, typhlocolitis. Lesion development was neither affected by antibiotics nor reproduced by infection with another enteric RNA virus, rotavirus. MNV-4 infection in Stat1-/- mice decreased expression of vascular endothelial growth factor (Vegf) receptor 3, Vegf-c, and Vegf-d and increased interferon (Ifn)-γ, tumor necrosis factor-α, and inducible nitric oxide synthase. However, anti-IFN-γ and anti-tumor necrosis factor-α antibody treatment did not attenuate the histologic lesions. Studies in Ifnαßγr-/- mice suggested that canonical signaling via interferon receptors did not cause MNV-4-induced disease. Infected Stat1-/- mice had increased STAT3 phosphorylation and expressed many STAT3-regulated genes, consistent with our findings of increased myeloid cell subsets and serum granulocyte colony-stimulating factor, which are also associated with increased STAT3 activity. In conclusion, in Stat1-/- mice, MNV-4 induces lymphatic lesions similar to those seen in Crohn disease as well as hepatitis, splenitis, and typhlocolitis. MNV-4-infected Stat1-/- mice may be a useful model to study mechanistic associations between viral infections, lymphatic dysfunction, and intestinal inflammation in a genetically susceptible host.

Personalized Bioactive Nasal Supports for Postoperative Cleft Rhinoplasty.

PURPOSE: After cleft lip and palate surgical procedures, patients often need nostril supports to help the reconstructed nostrils retain their shape during healing. Many postoperative nasal stents use a one-size-fits-all approach, in which a standard rubber tube retainer is trimmed and used to support the healing nares. The purpose of this study was to examine photogrammetry and 3-dimensional (3D) printing as a fabrication tool for postoperative patient-specific nasal supports that can be loaded with bioactive agents for localized delivery. MATERIALS AND METHODS: A "normal" right nostril injection mold was prepared from a left-sided unilateral cleft defect, and the negative-space impression was modeled using a series of photographs taken at different rotation angles with a commercial mobile phone camera. These images were "stitched" together using photogrammetry software, and the computer-generated models were reflected, joined, and digitally sculpted to generate hollow bilateral supports. Three-dimensional prints were coated with polyvinylpyrrolidone-penicillin and validated for their ability to inhibit Escherichia coli using human blood agar diffusion assays. RESULTS: The results showed that our approach had a high level of contour replication and the antibiotic coating was able to inhibit bacterial growth with a mean zone of inhibition of 15.15 ± 0.99 mm (n = 9) (P < .0001) in disc diffusion assays. CONCLUSIONS: Consumer-grade 3D printing displays potential as a fabrication method for postoperative cleft bilateral nasal supports and may support the surgically reconstructed internal contours. The results of this study suggest that such types of bioactive 3D prints may have potential applications in personalized drug-delivery systems and medical devices.

Gastroesophageal reflux disease: A clinical overview for primary care physicians.

OBJECTIVE: GERD is among the most common outpatient disease processes encountered by clinicians on a daily basis. This review provides insights about how to approach GERD in terms of disease management and treatment. METHODS: Review articles were searched using PUBMED and MEDLINE using criteria that included English language articles published in the last 5 years concerning studies carried out only in humans. The key words used in the searches were GERD, PPI, and erosive esophagitis. Recommendations from the American College of Gastroenterology are also included in this manuscript. RESULTS: The search resulted in ∼260 articles. The manuscript brings together and presents the results of recent recommendations from professional societies and recently published review articles on GERD. CONCLUSION: GERD is one of the most common diagnoses made by gastroenterologists and primary care physicians. It is important to recognize the typical and atypical presentations of GERD. This paper helps primary care physicians understand the disease's pathophysiology, and when, how, and with what to treat GERD before referring patients to gastroenterologists or surgeons.