"I Found Comfort in Exercising": Exploring Experiences With Exercise for Adults With Attention-Deficit/Hyperactivity Disorder.

Little is known about how adults with attention-deficit/hyperactivity disorder (ADHD) experience exercise, resulting in a lack of recommendations for supporting this population. We aimed to explore how adults with ADHD experience exercise as a management tool before and after diagnosis and how and why individuals experience issues related to exercise dependence. Fifteen active adults with a diagnosis of ADHD participated in semistructured interviews. Three overarching themes were identified: (a) exercise as a necessity for ADHD, reflecting the need to exercise before a formal ADHD diagnosis, and use of exercise as a management tool postdiagnosis; (b) goals and achievements to live by, reflecting how exercise patterns revolved around a need to make progress toward targets; and (c) activity or exercise: a roller coaster journey, covering the ups and downs of exercise journeys. This article highlights the importance of exercise for adults to manage ADHD and how this can be encouraged and supported.

Exercise Dependency and Overuse Injuries in Attention Deficit Hyperactivity Disorder.

ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is a common condition, but current medications have limitations, pushing a drive for alternative approaches. Different exercise-focused approaches have shown promise, but concern has also been raised about individuals with ADHD showing greater risk of addiction, including exercise dependency. Using an online survey, we examined current exercise practices, including exercise dependency and the presence of overuse injury, which could result from overexercising, in 114 adults with ADHD. We found that most were regularly exercising. None were classified as exercise dependent, but 38.9% were deemed symptomatic nondependent. Hyperactive-impulsive symptoms were a predictor of the level of exercise withdrawal experienced, and the co-occurrence of autism spectrum disorder was associated with greater risk of overuse injuries. The data indicate that ADHD may confer some greater risk of exercise dependency, aligning with previous studies investigating other addictions and suggesting further research is critical.

Investigating the Molecular Interactions of Quinoline Derivatives for Antibacterial Activity Against Bacillus subtilis: Computational Biology and In Vitro Study Interpretations.

Bacterial infections are evolving and one of the chief problems is emergence and prevalence of antibacterial resistance. Moreover, certain strains of Bacillus subtilis have become resistant to several antibiotics. To counteract this menace, the present work aimed to comprehend the antibacterial activity of synthesized two quinoline derivatives against Bacillus subtilis. Toxicity predictions via Protox II, SwissADME and T.E.S.T (Toxicity Estimation Software Tool) revealed that these derivatives were non-toxic and had little to no adverse effects. Molecular docking studies carried out in Schrodinger with two quinoline derivatives (referred Q1 and Q2) docked against selected target proteins (PDB IDs: 2VAM and1FSE) of B. subtilis demonstrated ideal binding energies (2VAM-Q1: - 4.63 kcal/mol and 2VAM-Q2: - 4.46 kcal/mol, and 1FSE-Q1: - 3.51 kcal/mol, 1FSE-Q2: - 6.34 kcal/mol). These complexes were simulated at 100 ns and the outcomes revealed their stability with slight conformational changes. Anti-microbial assay via disc diffusion method revealed zones of inhibition showing that B. subtilis was inhibited by both Q1 and Q2, with Q2 performing slightly better than Q1, pointing towards its effectiveness against this organism and necessitating further study on other bacteria in prospective studies. Thus, this study demonstrates that our novel quinoline derivatives exhibit antibacterial properties against Bacillus subtilis and can act as potent anti-bacterials.

Can Continuous Manufacturing of Topical Semisolids by Hot Melt Extrusion Soon Be a Reality?

For more than five decades, pharmaceutical manufacturers have been relying heavily on batch manufacturing that is a sequential, multistep, laborious, and time-consuming process. However, late advances in manufacturing technologies have prompted manufacturers to consider continuous manufacturing (CM) is a feasible manufacturing process that encompasses fewer steps and is less tedious and quick. Global regulatory agencies are taking a proactive role to facilitate pharmaceutical industries to adopt CM that assures product quality by employing robust manufacturing technologies encountering fewer interruptions, thereby substantially reducing product failures and recalls. However, adopting innovative CM is known to pose technical and regulatory challenges. Hot melt extrusion (HME) is one such state-of-the-art enabling technology that facilitates CM of diverse pharmaceutical dosage forms, including topical semisolids. Efforts have been made to continuously manufacture semisolids by HME integrating the principles of Quality by Design (QbD) and Quality Risk Management (QRM) and deploying Process Analytical Technologies (PAT) tools. Attempts have been made to systematically elucidate the effect of critical material attributes (CMA) and critical process parameters (CPP) on product critical quality attributes (CQA) and Quality Target Product Profiles (QTPP) deploying PAT tools. The article critically reviews the feasibility of one of the enabling technologies such as HME in CM of topical semisolids. The review highlights the benefits of the CM process and challenges ahead to implement the technology to topical semisolids. Once the CM of semisolids adopting melt extrusion integrated with PAT tools becomes a reality, the process can be extended to manufacture sterile semisolids that usually involve more critical processing steps.

Polymer coated polymeric microneedles for intravitreal delivery of dexamethasone.

The polymer coated polymeric (PCP) microneedles (MNs) is a novel approach for controlled delivery of drugs (without allowing release of the excipients) to the target site. PCP MNs was explored as an approach to deliver the drug intravitreally to minimize the risks associated with conventional intravitreal injections. The core MNs was fabricated with polyvinyl pyrrolidone K30 (PVP K30) and coating was with Eudragit E100. Preformulation studies revealed that the films prepared using Eudragit E 100 exhibited excellent integrity in the physiological medium after prolonged exposure. FTIR studies were performed to investigate the possible interaction between the API and the polymer. The PCP MNs fabricated with different drug loads (dexamethasone sodium phosphate) were subjected to in vitro drug release studies. The drug release from uncoated MNs was instantaneous and complete. On the other hand, a controlled release profile was observed in case of PCP MNs. Likewise, even in the ex vivo porcine eye model, the drug release was gradual into the vitreous humor in case of PCP MNs. The uncoated microneedles released all the drug instantaneously where the PCP MNs retarded the release up to 3 h.

Continuous Manufacturing of Oil in Water (O/W) Emulgel by Extrusion Process.

Pharmaceutical industries and drug regulatory agencies are inclining towards continuous manufacturing due to better control over the processing conditions and in view to improve product quality. In the present work, continuous manufacturing of O/W emulgel by melt extrusion process was explored using lidocaine as an active pharmaceutical ingredient. Emulgel was characterized for pH, water activity, globule size distribution, and in vitro release rate. Additionally, effect of temperature (25°C and 60°C) and screw speed (100, 300, and 600 rpm) on the globule size and in vitro release rate was studied. Results indicated that at a given temperature, emulgel prepared under screw speed of 300 rpm resulted in products with smaller globules and faster drug release.

Sublimation of Drugs from the Site of Application of Topical Products.

The objective of the project was to investigate the plausibility of active pharmaceutical ingredients (APIs) to undergo sublimation from topical application following evaporation of solvent. Topical formulations with different APIs were subjected to a sublimation screening test. The APIs in the selected topical products were found to undergo sublimation to a different extent. The salicylic acid topical product was found to undergo a significant loss due to sublimation. The extent of sublimation of salicylic acid was significantly greater at skin temperature compared to room temperature. When the APIs were subjected to the sublimation screening test in their neat form at 32 ± 1 °C, the natural log of the rate of sublimation decreased linearly with the standard enthalpy of sublimation of compound (R2 = 0.89). The formulation composition was found to have a significant impact on the extent of sublimation of the representative API, salicylic acid. The sublimation of APIs from the topical product was found to affect the mass balance studies in the case of the salicylic acid ointment. Furthermore, the results of the human studies agreed with the in vitro experimental results demonstrating the plausibility of loss of API due to sublimation from the site of application.

Polymer-Coated Polymeric (PCP) Microneedles for Controlled Dermal Delivery of 5-Fluorouracil.

Polymeric microneedles were prepared with Polyvinyl Pyrrolidone (PVP) K-30 using the mold casting technique. The core microneedles were coated with Eudragit E-100 by dip and spin method. The amount of 5-fluorouracil (FU) loaded in the core microneedles was 604 ± 35.4 µg. The coating thickness was 24.12 ± 1.12 µm. The objective was to deliver the 5-FU gradually in a controlled release manner at the target site in the sub-stratum corneum layer. This approach is anticipated to improve the safety and efficacy of topical melanoma treatment. The release of the drug was prolonged for up to 3 h from the polymer-coated polymeric (PCP) microneedles. The entire amount was found to release within 15 min in uncoated MNs. Likewise, the permeation of the drug from the uncoated microneedles was rapid, whereas the PCP microneedles were able to prolong the permeation up to 420 min. The PCP microneedles were subjected to stability studies at 25°C ± 2°C/60%RH, and 40°C ± 2°C/75%RH condition for 3 months. The formulations were found intact, and the release rate was not significantly different form the fresh formulation. The drug content was found to meet the acceptability criteria as well (98.12 ± 1.8% and 97.8 ± 2.1% at 25 and 40°C respectively after 3 months). Overall, this study demonstrated the feasibility of fabrication of PCP microneedles using Eudragit E100 for intraregional controlled delivery of drugs.

Polymer Coated Polymeric (PCP) Microneedles for Controlled Delivery of Drugs (Dermal and Intravitreal).

Microneedles are used to deliver drugs topically across the skin and mucous membranes. Dissolvable microneedles are made using soluble polymers, which disintegrates in the tissue and release the entire payload instantaneously including the polymer construct. Often, a slow release of drug into the tissue is desirable to overcome the severity of side effects at the site of administration as well as systemic adverse effects. In addition, controlled release of active pharmaceutical ingredient (API) only (not the excipients) is safe and effective particularly when the drug delivery is intended to sensitive organs like the eye. In this project, the feasibility of fabricating polymer coated polymeric (PCP) microneedles to achieve a gradual release of only the active ingredient from the device was investigated. The potential application of such PCP microneedles in the dermal and intravitreal drug delivery was also explored using animal tissue models. The PCP microneedles were found to be intact even after prolonged contact with the release medium. The time at which 50% (T50%) of dextran (10 K) was released in case of microneedles prepared using 20% of core polymer (PVP-K30) was about 15 min versus less than 5 min in the case of uncoated microneedles. Whereas when the core polymer concentration was increased to 50%, the T50% was increased to 90 min. The rate of release depended on the polymer molecular weight grade. The rate of drug release was not influenced by the total amount of concentration of dextran. The PCP microneedles of lidocaine hydrochloride could constantly release the drug for up to 9 h in the skin tissue. Likewise, the PCP microneedles infused voriconazole, intravitreally for 6 h.

Evaluation of antifungal activity of six children's toothpaste on Candida albicans isolated from early childhood caries patients.

BACKGROUND: Early childhood caries (ECC) is an aggressive, destructive form of dental caries that affects the children younger than 6 years of age. Candida is known to increase the adherence of Streptococcus mutans to the oral biofilm and produce acids that cause tooth demineralization. AIM OF THE STUDY: To evaluate the efficacy of six commercially available children's toothpaste on clinical isolates of Candida albicans obtained from ECC patients. MATERIALS AND METHODS: The study population comprised 60 children aged 3-6 years having ECC. Samples were divided into six groups comprising ten children in each group. Samples were collected using sterile cotton swabs, inoculated on Sabouraud dextrose agar, and incubated at 37°C for 24 h. Species identification was done by germ tube test and growth on corn meal agar. After the confirmed growth of C. albicans, the six commercially available children's toothpaste namely Organic Children's Coconut Oil Toothpaste®, Aloe Dent Children's Toothpaste®, Patanjali Dant Kanti Junior Toothpaste®, Colgate Kids Toothpaste®, Pediflor Kids Toothpaste®, and Crest Pro-Health Stages Kids Toothpaste® and distilled water as control group were subjected for antifungal activity of C. albicans. Agar plates were incubated at 37°C for 48 h, and the diameter of the zones of inhibition was measured and recorded. Data were tabulated and statistical analysis was done using Statistical Package for the Social Science (16.0) version. RESULTS: Pediflor kids toothpaste® showed maximum antifungal activity and Aloe Dent children's toothpaste® showed minimum antifungal activity. CONCLUSION: All brands of children's toothpaste show antifungal activity against Candida albicans.

Oligoamnios and Perinatal Outcome.

OBJECTIVES: We aimed at evaluating the predictive value of amniotic fluid index ≤5 on perinatal outcome in terms of effect on cardiotocography, mode of delivery, meconium in liquor, birth weight, fetal distress, APGAR score at birth and neonatal admission to ICU. METHODS: This is a prospective study of 308 antenatal women admitted to labor ward of MIMS during February 2014-December 2015 with gestational ages between 34 and 41 weeks. All women enrolled were subjected to history taking, examination, AFI estimation and compared between those with AFI ≤5 from rest. RESULTS: The non-reactive CTG, cesarean section rate due to fetal distress, low birth weight, APGAR score <7 and NICU admission were significantly high among those with oligoamnios than the control group. CONCLUSION: Oligoamnios has a significant correlation with adverse perinatal outcome.

Application of Microneedle Arrays for Enhancement of Transdermal Permeation of Insulin: In Vitro Experiments, Scaling Analyses and Numerical Simulations.

The aim of this investigation is to study the effect of donor concentration and microneedle (MN) length on permeation of insulin and further evaluating the data using scaling analyses and numerical simulations. Histological evaluation of skin sections was carried to evaluate the skin disruption and depth of penetration by MNs. Scaling analyses were done using dimensionless parameters like concentration of drug (C t/C s), thickness (h/L) and surface area of the skin (S a/L (2)). Simulation studies were carried out using MATLAB and COMSOL software to simulate the insulin permeation using histological sections of MN-treated skin and experimental parameters like passive diffusion coefficient. A 1.6-fold increase in transdermal flux and 1.9-fold decrease in lag time values were observed with 1.5 mm MN when compared with passive studies. Good correlation (R (2) > 0.99) was observed between different parameters using scaling analyses. Also, the in vitro and simulated permeations profiles were found to be similar (f 2 ≥ 50). Insulin permeation significantly increased with increase in donor concentration and MN length (p < 0.05). The developed scaling correlations and numerical simulations were found to be accurate and would help researchers to predict the permeation of insulin with new dimensions of MN in optimizing insulin delivery. Overall, it can be inferred that the application of MNs can significantly enhance insulin permeation and may be an efficient alternative for injectable insulin therapy in humans.

Primary tuberculous osteomyelitis of the mandible: A rare case report.

Tuberculosis (TB) has become a rare disease in the developed countries but it is still a serious problem in developing countries. Incidence of tuberculous osteomyelitis of the jaw bones is very low. This rare incidence is the primary reason that this lesion gets mis-diagnosed many times. Here we report the diagnosis, treatment and follow-up of a case, which is a classical presentation of tuberculous osteomyelitis of mandible. Primary tuberculous osteomyelitis is a very rare entity but in the recent times, increased incidence of TB as a coinfection of HIV, has posed a big challenge in developing countries. If not diagnosed, at the right time, this can lead to serious complications like internal organ damage, tuberculous meningitis etc., Early diagnosis of tuberculous osteomyelitis will certainly reduce the morbidity of this disease condition.

Maxillary movement in cleft patients treated with internal tooth borne distractor.

Cleft lip and palate is associated with maxillary hypoplasia and retrognathism. Surgery and distraction have been the most common treatment approaches used. The aim of this study was to objectively assess the quantum and direction of movement of the anterior maxilla in cleft patients treated with an internal tooth borne distractor. A prospective clinical study design was followed in which 8 consecutive patients with cleft maxillary hypoplasia were included in the age range of 15-25 years. All patients had undergone secondary alveolar bone grafting earlier. Anterior maxillary distraction was performed using a tooth borne appliance in all 8 patients after necessary osteotomy. Lateral cephalograms were obtained preoperatively, predistraction and postdistraction. The angular and linear change at the maxillary anterior segment, rotation of the palatal plane, mandibular plane, increase in lower facial height and vertical changes of the anterior and posterior dentoalveolar segments were measured. The movement of the anterior maxillary segment was demonstrated anteriorly and superiorly in all the patients. The anterior and posterior dentoalveolar heights were increased post-distraction. There was also an increase in lower anterior facial height and the mandibular plane angle. Predictable superior and anterior movement of the anterior maxilla along with significant increase in palatal length could be achieved with the internal tooth borne distractor leading to remarkable improvement in esthetics and better function.