Malignant transformation of keratocystic odontogenic tumor: two case reports.

INTRODUCTION: Keratocystic odontogenic tumors (KCOTs) are cystic tumours originating from the dental lamina of the maxilla and mandible that are lined with keratinized epithelium. While benign, they can be locally destructive and have a high recurrence rate despite treatment. Rarely, KCOTs may undergo malignant transformation into Primary Intraosseous Squamous Cell Carcinoma (PIOSCC). CASE REPORT: This study reports the clinical findings, radiological scans and histopathology of 2 patients with KCOTs that underwent malignant transformation into PIOSCC. DISCUSSION: A comprehensive literature review was performed to similar reports documenting the malignant transformation of KCOTs. The potential for KCOTs to undergo malignant change should prompt oral maxillofacial surgeons and otolaryngologists to exercise a high index of suspicion when treating these lesions. Patients persisting with unresolved disease after treatment should be investigated for malignant transformation. Detailed histopathological examination of KCOT specimens is recommended to detect small foci of SCC which may be present in the epithelium.

Two-Stage Supramolecular Self-Assembly-Directed Collagen-Peptide-Decorated Liposomal Complexes of Curcumin Microspheres with Enhanced Solubility and Bioavailability.

Green formulations of phytonutrients with enhanced solubility and bioavailability are of great significance in nutrition therapy. In the present contribution, we hypothesized that the collagen peptides could be a safe, natural, food-grade, and cost-effective functional agent for the surface decoration and stabilization of liposomes in powder form and hence a "green" solution for the oral delivery of phytonutrients. The present study reports a two-stage supramolecular self-assembly-directed process for the preparation of collagen peptide-decorated liposomal complexes of curcumin (CCL) [10% (w/w)] as microspheres (125 ± 25 µm) with improved solubility (1.46 × 105-fold) and sustained-release properties under gastrointestinal pH conditions. The molecular self-assembly of collagen peptides around the lipid bilayers and the various noncovalent interactions and conformational changes leading to the supramolecular assembly to act as a matrix for the encapsulation of lipid vesicles of curcumin were clear from the spectroscopic studies (UV-vis, fluorescence, FTIR, and circular dichroism). Further investigation of pharmacokinetics following a randomized double-blinded controlled trial on healthy volunteers (n = 15) demonstrated that the oral administration of 2.5 g of CCL sachet (250 mg of curcumin) enhanced the plasma concentration (Cmax: 118 vs. 4.3 ng/mL), the elimination half-life (4.2 vs. 0.7 h), and bioavailability as per the area under the curve over 12 h [AUC0-12h (CCL) = 506·8 vs. AUC0-12h (C95) = 9.47 (53-fold)], when the plasma concentration of curcumin was estimated with triple quadruple tandem mass spectrometry (UPLC-ESI-MS/MS).

Micelle/Hydrogel Composite as a "Natural Self-Emulsifying Reversible Hybrid Hydrogel (N'SERH)" Enhances the Oral Bioavailability of Free (Unconjugated) Resveratrol.

The poor oral bioavailability, rapid biotransformation to less active metabolites, and fast elimination from systemic circulation have been identified as the major limitations responsible for the clinical insignificance of many drug candidates and phytonutrients. Despite the technological advancements in the nanoformulations of synthetic drugs, there exist many challenges for nutritional therapy, due to the regulatory issues, use of high levels of synthetic emulsifiers and polymers, low stability, low loading levels, mainly liquid state, etc. Herein, we report the characterization and human pharmacokinetics of a natural self-emulsifying hybrid-hydrogel formulation of trans-resveratrol prepared by uniformly impregnating resveratrol micelles into the fenugreek galactomannan hydrogel scaffold to form a water-soluble micelle/hydrogel composite in powder form (RF-20). Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), particle size analysis by dynamic light scattering (DLS), and transmission electron microscopy (TEM) demonstrated the uniform impregnation of resveratrol micelles within the galactomannan hydrogel matrix to form a soluble (average particle size of 172.0 ± 10.4 nm and -21.0 ± 2.5 mV zeta potential) and amorphous powder form with smooth and translucent surface morphology for RF-20, with no chemical alterations. Upon pharmacokinetic studies on healthy human subjects (n = 16) following a randomized, double-blinded, placebo-controlled, 2-arm, 4-sequence crossover design and tandem mass spectrometry (UPLC-ESI-MS/MS), 80 mg of trans-resveratrol from RF-20 provided enhanced free resveratrol bioavailability and pharmacokinetic properties compared to the unformulated resveratrol with 98% purity. The enhancement in bioavailability was more when supplemented in sachet (12.98-fold) form than the capsule (10.48-fold) with improved absorption (C max = 50.97 ± 15.82 ng/mL), circulation half-life (t 1/2 = 7.01 ± 1.44 h), and sustained delivery (T max = 4.71 ± 0.73 h), as compared to the unformulated form (C max = 15.07 ± 5.10 ng/mL; t 1/2 = 1.58 ± 0.65 h; T max = 1.21 ± 0.42 h).

Enhanced Bioavailability and Pharmacokinetics of a Natural Self-Emulsifying Reversible Hybrid-Hydrogel System of Quercetin: A Randomized Double-Blinded Comparative Crossover Study.

Despite the vast array of health beneficial pharmacological effects, the bioavailability of the dietary flavonoid quercetin was found to be poor due to insolubility, incompatibility, and rapid biotransformation. Herein, we investigated the solubility, morphology, particle size, stability, in vitro release, and human pharmacokinetics of a hybrid-hydrogel formulation of quercetin (FQ-35) using fenugreek galactomannans as the hydrogel scaffold. Physicochemical characterization revealed that the crystalline quercetin was well encapsulated in the hydrogel matrix to form translucent microgel particles of FQ-35 with enhanced solubility (96-fold). The mean particle size was found to be 183.6 ± 42.7 nm with a zeta potential of 35.1 ± 3.8 mV. Pharmacokinetic investigation on healthy volunteers (N = 16) employing tandem mass spectrometric (ultra-performance liquid chromatography-electrospray tandem mass spectrometry) measurements of the concentration of free (unconjugated) and conjugated quercetin metabolites revealed an 18.6-fold improvement in free (unconjugated) quercetin bioavailability and 62-fold improvement in total quercetin (sum of free and conjugated) bioavailability, compared to the unformulated quercetin extracted from Sophora japonica. In summary, the natural self-emulsifying reversible hybrid-hydrogel delivery system was found to offer significant solubility, stability, and bioavailability of quercetin upon single-dose oral administration.

Surface-engineered liposomal particles of calcium ascorbate with fenugreek galactomannan enhanced the oral bioavailability of ascorbic acid: a randomized, double-blinded, 3-sequence, crossover study.

The antioxidant, anti-inflammatory, immunomodulating, anti-thrombotic, and antiviral effects along with its protective effects against respiratory infections have generated a great interest in vitamin C (vitC) as an attractive functional/nutraceutical ingredient for the management of COVID-19. However, the oral bioavailability and pharmacokinetics of vitC have been shown to be complex and exhibit dose-dependent non-linear kinetics. Though sustained-release forms and liquid liposomal formulations have been developed, only marginal enhancement was observed in bioavailability. Here we report a novel surface-engineered liposomal formulation of calcium ascorbate (CAAS), using fenugreek galactomannan hydrogel in powder form, and its pharmacokinetics following a randomized, double-blinded, single-dose, 3-way crossover study on healthy human volunteers (n = 14). The physicochemical characterization and in vitro release studies revealed the uniform impregnation of CAAS liposomes within the pockets created by the sterically hindered galactomannan network as multilaminar liposomal vesicles with good encapsulation efficiency (>90%) and their stability and sustained-release under gastrointestinal pH conditions. Further human studies demonstrated >7-fold enhancement in the oral bioavailability of ascorbate with a significant improvement in pharmacokinetic properties (C max, T max, T 1/2, and AUC), compared to the unformulated counterpart (UF-CAAS) when supplemented at an equivalent dose of 400 mg of CAAS as tablets and capsules.

The Rights of Persons with Disabilities Act 2016: Mental Health Implications.

India's ratification of the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) necessitated the need for a rights-based, biopsychosocial model of disability, which was endorsed in the Rights of Persons with Disabilities (RPwD) Act, 2016. This article examines the Act, its rules, and guidelines provided by the Government of India, from a mental health perspective, and compares it to its predecessor, the Persons with Disabilities (PwD) Act, 1995. The RPwD Act provides clearer definitions of various constructs, a greater focus on rights of PwD, and guidelines for assessment and certification of disabilities. There is, however, an underemphasis on mental illnesses in the reservation and legal decision making, and a move toward centralizing the process of disability certification. Also, there is a lack of clarity about screening instruments to be used, resource allocation to implement the provisions, and the guidelines for inclusive education. This article suggests recommendations that could strengthen some of these provisions.

Laryngeal inflammatory myofibroblastic tumor (IMT): a case report and review of the literature.

BACKGROUND: This case report is interesting as cases of children with laryngeal inflammatory myofibroblastic tumor are not common and previously had been presented as isolated case reports. This is the first case report in Asia describing a laryngeal inflammatory myofibroblastic tumor and its removal using an endoscopic approach. CASE PRESENTATION: Our patient is a 12-year-old Malay girl from Singapore who presented with hoarseness without respiratory distress. The initial impression was that of a granuloma or a papilloma. We did a biopsy, which confirmed the histology to be inflammatory myofibroblastic tumor, and a magnetic resonance imaging scan showed a contrast-enhanced lesion. The lesion was excised completely using an endoscopic approach. The child was discharged well on the first postoperative day and she has been on follow-up for a year in the clinic. CONCLUSIONS: This report highlights the importance of understanding the differential diagnosis for a child with hoarseness. It is not uncommon for a pediatrician, a general practitioner, and a pediatric otolaryngologist to see a child presenting with hoarseness. In most cases, the diagnosis made would be screamer's nodules, which is commonly seen in children. In a small group, recurrent respiratory papillomatosis form the diagnosis. Over the past few years, the cases of recurrent respiratory papillomatosis have decreased significantly. Laryngeal tumors are not common in children. However, we must maintain a high index of suspicion when we have a child with hoarseness who does not improve with speech therapy and watchful waiting. In such situations, a stroboscope is usually necessary to diagnose the voice problems and to rule out pathological conditions such as laryngeal tumors. If left untreated, the lesion can grow with time and result in a life-threatening airway condition. We also demonstrate our endoscopic technique in this report, and it has proven to be safe with no increased recurrence and much lower morbidity.

Paediatric obstructive sleep apnoea: is a polysomnogram always necessary?

Obstructive sleep apnoea (OSA) is a common entity in children, most present with sleep disturbances such as snoring, choking during sleep, enuresis, restless sleep, or apnoeic spells. Other symptoms include poor school performance, hyperactivity, failure to thrive, heart failure and cor pulmonale. Most authors would concur that the polysomnogram (PSG) is the gold standard for the diagnosis of OSA, and that adenotonsillectomy is the surgical procedure of choice, with high curative rates and relatively low morbidity. Close post-operative monitoring of all children with OSA cannot be over-emphasized. The focus has been, traditionally, to anticipate post-operative airway and respiratory complications in this group of children. We present 73 children with clinical OSA and 36 children with proven OSA on PSG, with only one child having respiratory complications (mixed apnoea), and all with uneventful recovery. In view of our low complication rates, low post-operative morbidity, cost and facility factor, the need for a mandatory overnight PSG pre-operatively is questioned, and clinical criteria for performing a PSG preoperatively are suggested.

Preauricular sinuses in the pediatric population: techniques and recurrence rates.

AIM: To review the outcomes of two surgical techniques in the management of preauricular sinus in the pediatric population. METHODS: The clinical records of pediatric patients who underwent surgical excision of preauricular sinus in the Department of Otolaryngology of KK Children's and Women's Hospital between January 1997 and March 2009 were retrospectively reviewed. Patients were categorized into two groups, based on the method used for sinus tract visualization or delineation: (1) Microscope group and (2) methylene blue dye and probe group. The latest information on recurrence of preauricular sinus and complications after surgery were updated by phone interview. RESULTS: 208 out of 305 preauricular sinuses were included in this study (n=114 in microscope group; n=94 in methylene blue dye and probe group). 97 cases were excluded as these patients were not contactable by phone or had inadequate data from the clinical records. The mean age of the patients is 6.5 years old. The overall recurrence rate was 2.4% (95% confidence interval (CI) 0.010-0.055) and the overall complication rate was 6.3% (CI 0.037-0.104). Surgical excision with microscope guidance had significantly lower recurrence rate (0.9%) compared to surgical excision with methylene blue dye and probe guidance (4.3%), with an odds ratio of 28.4 (CI 1.22-659.99, P=0.037). The complication rates were not statistically significant between the two groups. The recurrence and complication rates were not significantly affected by race, gender, sex, location of sinus, indication for surgery, history of previous sinus excision, presence of infection during surgery and duration of surgery. CONCLUSION: Surgical excision of preauricular sinus under microscope guidance and under methylene blue and probe guidance in our series had very low overall recurrence and complication rates compared to that reported in the literature. The microscope group had a lower recurrence rate in comparison to that of the methylene blue and probe group.

Allergic rhinitis and non-allergic rhinitis in children in the tropics: prevalence and risk associations.

BACKGROUND: The age-related comparative prevalence of allergic rhinitis (AR) and non-allergic rhinitis (NAR) in children is poorly defined. We aimed to characterize AR and NAR in children. METHODS: This study enrolled children with chronic rhinitis who presented to a tertiary paediatric center for a diagnostic skin prick test (SPT). Parents completed a medical history questionnaire for their child, including disease activity for asthma and rhinitis. Sociodemographic data was obtained and all participants underwent a common inhalant SPT panel. A positive SPT indicated AR. RESULTS: From March 2001 to March 2009, 6,660 children (64% male) were enrolled (aged 6 months to 19 years, mean 7.82 years). Only 3.7% (249) of the children were <2 years old, and almost 30% of these had AR. Most children with AR (73%) presented after age 6. Males were more likely to have AR (vs. NAR) (OR 1.5; CI 1.39-1.77). Antihistamine and salbutamol use did not differ between children with AR and NAR. Children with AR were more likely to require adjunct therapy with inhaled corticosteroids (51.2% vs. 43.2%, P < 0.001), have drug hypersensitivity (especially antipyretic drugs) (2.5% vs. 1.3%, P = 0.384) or an asthma admission (9.1% vs. 6.0%, P < 0.001). CONCLUSIONS: AR is more common in male children, is relatively rare below the age of 2 years, and accounts for two-thirds of all childhood chronic rhinitis and 73.3% of all chronic rhinitis in school-aged children (≥6 years old). Children with AR have more severe rhinitis symptoms and more often suffer from asthma-related events and admissions.

Aeroallergen sensitization in pediatric allergic rhinitis in Singapore: is air-conditioning a factor in the tropics?

Singapore is a unique blend of a tropical environment with a high standard of hygiene and public health care. The objective was to define the prevalence, clinical characteristics, and environmental risk factors of specific aeroallergen sensitization in pediatric allergic rhinitis patients in this unique environment. The method adopted was a retrospective analysis of allergic rhinitis patients, undergoing aeroallergen skin prick testing (SPT), in the outpatient specialty clinic of the KK Children's hospital, from July 2001 to June 2002. A total of 202 patients were included, 161 (80%) males, 167 (83%) Chinese, age mean 7.6 yr (range 2-14 yr). The most prevalent clinical symptoms were: watery rhinorrhea 61%, blocked nose 61%, sneezing 52%, snoring 17%, and epistaxis 12%. SPT results were positive for house dust mites in 97% of children, pets (20%), molds (19%), pollens (15%), and kapok (10%). Mold sensitization was significantly more prevalent in households without air-conditioning (aircon), 49% vs. 10% with aircon (odds ratio 9.4, 95% CI 3.8-22.9). Polysensitization (sensitization to three or more allergens) was similarly more prevalent in households without aircon, 51% vs. 14% with aircon (odds ratio 6.4, 95% CI 2.8-14.7). It was concluded that indoor aeroallergen sensitization is the major associated factor with clinical allergic rhinitis in children in Singapore. Patients living in households without air-conditioning are at increased risk of mold sensitization and polysensitization.

Bimodal skin reactivity to histamine in atopic children in Singapore: influence of specific sensitizations.

Histamine skin prick test (SPT) is used as the 'golden standard' for positive control in in vivo immediate type hypersensitivity testing. The skin reactivity to histamine can, however, be modulated by a bevy of extraneous factors. We aimed to define whether histamine skin reactivity in atopic children in Singapore is influenced by age, ethnic origin, gender, environmental exposure or specific sensitization patterns. A retrospective analysis of children, with specific aeroallergen sensitization (as measured by at least one allergen-specific SPT with a wheal size > 3 mm compared with the negative control) from the outpatient speciality clinic of the KK Children's Hospital, during 06/2002-06/2003. A total of 315 patients were included, 235 (75%) were males, 252 (80%) were Chinese, age mean was 7.7 yr (range: 2-15). Patients were referred to the SPT with a diagnosis of one or more of: allergic rhinitis 287 (91%), asthma 112 (36%) or atopic dermatitis 60 (19%). The mean histamine response showed a bimodal distribution, independent of age, ethnic origin, gender or phenotypical expression of allergic disease. Histamine skin reactivity was higher in atopic patients with polysensitization (mean 5.0 mm vs. 2.9 mm in monosensitized patients, p < 0.001), and in patients with mould sensitization (mean 5.1 mm vs. 3.3 mm in patient not sensitized to moulds, p < 0.001). The presence of passive smoking increased the likelihood of a diminished histamine skin response. Histamine skin response data strongly suggested the presence of two heterogeneous subpopulations. Children with polysensitization and mould sensitization were more likely to show a large significant histamine response, whereas children with passive smoke exposure, showed a diminished skin reactivity to histamine.