Reverse Engineering and 3D Printing of Medical Devices for Drug Delivery and Drug-Embedded Anatomic Implants.

In recent years, 3D printing (3DP) has advanced traditional medical treatments. This review explores the fusion of reverse engineering and 3D printing of medical implants, with a specific focus on drug delivery applications. The potential for 3D printing technology to create patient-specific implants and intricate anatomical models is discussed, along with its ability to address challenges in medical treatment. The article summarizes the current landscape, challenges, benefits, and emerging trends of using 3D-printed formulations for medical implantation and drug delivery purposes.

Central Retinal Artery Occlusion with Concomitant Intracranial Hemorrhage Secondary to Streptococcus Gordonii Endocarditis.

Purpose: To report a case of central retinal artery occlusion (CRAO) associated with subacute Streptococcus gordonii endocarditis secondary to a dental infection. Observations. A 27-year-old male presented with acute monocular vision loss in the setting of a stroke and seizure. A fundus exam revealed macular whitening and a cherry-red spot. Edema of the inner retinal layers was confirmed on macular optical coherence tomography, consistent with CRAO. Initial imaging (carotid Doppler, EKG, and transthoracic echocardiography) and a comprehensive laboratory workup did not reveal an etiology for the stroke or vision loss. Brain magnetic resonance imaging showed T1 hyperintensity with surrounding edema, which prompted a workup for possible septic emboli versus occult malignancy. Subsequent blood cultures led to the detection and diagnosis of Streptococcus gordonii endocarditis. It was subsequently revealed that the patient had self-extracted his molar two months prior to the onset of symptoms. Conclusions: Endocarditis has been associated with Roth spots and inflammatory findings in the posterior segment. However, CRAO caused by vegetal septic embolism is rare. To our knowledge, this represents the first reported case of endocarditic CRAO with Streptococcus gordonii confirmed as the causative microbe. Retinal vascular occlusion in a young patient with no distinct risk factors should prompt a comprehensive dental history and infectious workup, with consideration given to early transesophageal echocardiography.

PROMIS Utilization in Pediatric Orthopaedics: A Scoping Review.

BACKGROUND: The lack of a common patient-reported outcome metric used among the orthopaedic population is a problem that has been previously identified by the American Academy of Orthopaedic Surgeons. The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed by the National Institute of Health with the goal of creating a precise and efficient measurement tool for patient-reported symptoms, functioning, and health-related quality of life to be used in clinical research. A study summarizing its use in the pediatric orthopaedic population has not been previously performed. METHODS: We performed a literature search of Ovid Medline, Embase, Scopus, and the Cochrane Central Register of Controlled Trials from 2010 to August 2021. There were 1961 unique citations included after the removal of 1756 duplicates. After initial screening, 183 studies were screened under full-text review leaving a final number of 51 studies included in this scoping review. RESULTS: Pediatric PROMIS studies were grouped by body part or sub-speciality: "Hand and Upper Extremity" (25.5%, n=13), "Sports" (23.5%, n=12), "Spine" (13.7%, n=7), "Trauma" (13.7%, n=7), "General Pediatric Orthopaedics" (11.8%, n=6), "Lower Extremity" (9.8%, n=5), and "Orthopaedic Oncology" (2%, n=1). An increase in studies utilizing PROMIS was seen throughout the study period with only 3 studies published from 2013 to 2016 to 39 in 2020 and 2021 alone. The 3 most frequently used pediatric PROMIS domains were Pain Interference (76.5%, n=39/51), Mobility (60.8%, n=31/51), and Upper Extremity (54.9%, n=28/51). 64.3% (n=9/14) of the included studies which reported on the floor effects of Pain Interference exhibited a significant floor effect. In all, 77.8% (n=7/9) of the included studies which reported on ceiling effects of Upper Extremity exhibited a significant ceiling effect. CONCLUSION: The use of PROMIS increased significantly since the first publication in 2013 suggesting orthopaedic providers have increasingly utilized PROMIS in their day-to-day practice as an outcome measure. Ceiling and floor effects were prominent in several of the included domains (Pain Interference and Upper Extremity). Overall, PROMIS measures are efficient, reliable, and effective to use. LEVEL OF EVIDENCE: IV.

Restriction of intracellular Salmonella replication by restoring TFEB-mediated xenophagy.

Macroautophagy/autophagy functions as a part of the innate immune system in clearing intracellular pathogens. Although this process is well known, the mechanisms that control antibacterial autophagy are not clear. In this study we show that during intracellular Salmonella typhimurium infection, the activity of TFEB (transcription factor EB), a master regulator of autophagy and lysosome biogenesis, is suppressed by maintaining it in a phosphorylated state on the lysosomes. Furthermore, we have identified a novel, antibacterial small molecule autophagy (xenophagy) modulator, acacetin. The xenophagy effect exerted by acacetin occurs in an MTOR (mechanistic target of rapamycin kinase)-independent, TFEB-dependent manner. Acacetin treatment results in persistently maintaining active TFEB in the nucleus and also in TFEB mediated induction of functional lysosomes that target Salmonella-containing vacuoles (SCVs). The enhanced proteolytic activity due to deployment of lysosomes results in clamping down Salmonella replication in SCVs. Acacetin is effective as a xenophagy compound in an in vivo mouse model of infection and reduces intracellular Salmonella burden. ABBREVIATIONS: 3-MA: 3-methyladenine; BafA1: bafilomycin A1; CFU: colony-forming units; DQ-BSA: dye quenched-bovine serum albumin; EEA1: early endosome antigen 1; FITC: fluorescein isothiocyanate; FM 4-64: pyridinium,4-(6-[4-{diethylamino}phenyl]-1,3,5-hexatrienyl)-1-(3[triethylammonio] propyl)-dibromide; GFP: green fluorescent protein; LAMP1: lysosomal associated membrane protein 1; MAPILC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; RFP: red fluorescent protein; SCVs: Salmonella-containing vacuoles; SD: standard deviation; SDS: sodium dodecyl sulfate; SEM: standard mean error; SQSTM1: sequestosome 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB.

Modulation of Autophagy by a Small Molecule Inverse Agonist of ERRα Is Neuroprotective.

Mechanistic insights into aggrephagy, a selective basal autophagy process to clear misfolded protein aggregates, are lacking. Here, we report and describe the role of Estrogen Related Receptor α (ERRα, HUGO Gene Nomenclature ESRRA), new molecular player of aggrephagy, in keeping autophagy flux in check by inhibiting autophagosome formation. A screen for small molecule modulators for aggrephagy identified ERRα inverse agonist XCT 790, that cleared α-synuclein aggregates in an autophagy dependent, but mammalian target of rapamycin (MTOR) independent manner. XCT 790 modulates autophagosome formation in an ERRα dependent manner as validated by siRNA mediated knockdown and over expression approaches. We show that, in a basal state, ERRα is localized on to the autophagosomes and upon autophagy induction by XCT 790, this localization is lost and is accompanied with an increase in autophagosome biogenesis. In a preclinical mouse model of Parkinson's disease (PD), XCT 790 exerted neuroprotective effects in the dopaminergic neurons of nigra by inducing autophagy to clear toxic protein aggregates and, in addition, ameliorated motor co-ordination deficits. Using a chemical biology approach, we unrevealed the role of ERRα in regulating autophagy and can be therapeutic target for neurodegeneration.

A novel autophagy modulator 6-Bio ameliorates SNCA/α-synuclein toxicity.

Parkinson disease (PD) is a life-threatening neurodegenerative movement disorder with unmet therapeutic intervention. We have identified a small molecule autophagy modulator, 6-Bio that shows clearance of toxic SNCA/α-synuclein (a protein implicated in synucleopathies) aggregates in yeast and mammalian cell lines. 6-Bio induces autophagy and dramatically enhances autolysosome formation resulting in SNCA degradation. Importantly, neuroprotective function of 6-Bio as envisaged by immunohistology and behavior analyses in a preclinical model of PD where it induces autophagy in dopaminergic (DAergic) neurons of mice midbrain to clear toxic protein aggregates suggesting that it could be a potential therapeutic candidate for protein conformational disorders.

Low amplitude dorsal ulnar cutaneous nerve sensory nerve action potential from cross over innervation. Can nerve ultrasound help?

The ulnar dorsal aspect of the hand is predominantly innervated by the dorsal ulnar cutaneous nerve with variable input from the superficial radial cutaneous nerve. This cross innervation can cause difficulty in interpreting low amplitude sensory nerve action potential for the dorsal ulnar cutaneous nerve particularly when facing suspected ulnar neuropathyat the elbow. In three subjects with low dorsal ulnar cutaneous sensory nerve action potential amplitude due to cross over with the superficial radial nerve, we compared amplitude with nerve circumference and fascicular count as measured by ultrasound. Dorsal ulnar cutaneous nerve circumference was significantly smaller where there was low sensory nerve action potential amplitude and showed fewer fascicles. Nerve ultrasonography may be a useful additional test modality to determine if low dorsal ulnar cutaneous nerve amplitude is physiological.

Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study.

BACKGROUND: Peripheral neuropathy (PN) due to paclitaxel is a common dose-limiting toxicity with no effective prevention or treatment. We hypothesize that continuous-flow limb hypothermia can reduce paclitaxel-induced PN. PATIENTS AND METHODS: An internally controlled pilot trial was conducted to investigate the neuroprotective effect of continuous-flow limb hypothermia in breast cancer patients receiving weekly paclitaxel. Patients underwent limb hypothermia of one limb for a duration of 3 h with every paclitaxel infusion, with the contralateral limb used as control. PN was primarily assessed using nerve conduction studies (NCSs) before the start of chemotherapy, and after 1, 3, and 6 months. Skin temperature and tolerability to hypothermia were monitored using validated scores. RESULTS: Twenty patients underwent a total of 218 cycles of continuous-flow limb hypothermia at a coolant temperature of 22°C. Continuous-flow limb hypothermia achieved mean skin temperature reduction of 1.5 ± 0.7°C and was well tolerated, with no premature termination of cooling due to intolerance. Grade 3 PN occurred in 2 patients (10%), grade 2 in 2 (10%), and grade 1 in 12 (60%). Significant correlation was observed between amount of skin cooling and motor nerve amplitude preservation at 6 months (p < 0.0005). Sensory velocity and amplitude in the cooled limbs were less preserved than in the control limbs, but the difference did not attain statistical significance. One patient with a history of diabetes mellitus had significant preservation of compound muscle action potential in the cooled limb on NCS analysis. CONCLUSION: This study suggests that continuous limb hypothermia accompanying paclitaxel infusion may reduce paclitaxel-induced PN and have therapeutic potential in select patients and warrants further investigation. The method is safe and well tolerated.

Nerve ultrasound in electrophysiologically verified tarsal tunnel syndrome.

INTRODUCTION: Tarsal tunnel syndrome (TTS) arises from tibial nerve damage under the flexor retinaculum of the fibro-osseus tunnel at the medial malleolus. It is notoriously difficult to diagnose, as many other foot pathologies result in a similar clinical picture. We examined the additional value of nerve ultrasound in patients with tarsal tunnel syndrome confirmed by nerve conduction. METHODS: We performed a retrospective analysis of nerve ultrasound changes in electrophysiologically confirmed TTS spanning our records from 2007 to 2015. RESULTS: Nine feet with TTS were identified, all of which showed abnormal nerve ultrasound findings, which in 6 feet, led to identification of the underlying cause. CONCLUSIONS: This study shows that nerve ultrasound is abnormal in all cases of electrophysiologically verified TTS. The pattern of nerve abnormality is varied. This, and the fact that in the majority of patients causation was identified, suggests nerve ultrasound should form part of standard work-up for TTS. Muscle Nerve 53: 906-912, 2016.

Dentigerous Cysts of Maxillofacial Region- Clinical, Radiographic and Biochemical Analysis.

BACKGROUND: Dentigerous cyst is the second most common type of odontogenic cysts that encloses the crown of an unerupted tooth by expansion of its follicle due to the collection of cystic fluid. In view of the capability of these lesions attaining a marked size if not diagnosed early and treated properly, the present study was done based on the clinical and radiographic presentation of the dentigerous cyst in addition to the analysis of the cystic contents. OBJECTIVE: The present study reported 14 cases of dentigerous cysts (DC) with their incidence and relative distribution of the maxillofacial region along with the clinical and radiographic features and biochemical analysis of cystic fluid. METHOD: The study was conducted at Sri Govind Tricentenary Dental College, Hospital and Research Institute, Gurgaon, Haryana for a period of one year and six months. A detailed case history and thorough clinical examination was done for the patients who were provisionally found to have odontogenic cysts. Necessary radiographs, aspiration of the cystic fluid and incisional biopsy were performed to the 14 patients who were provisionally diagnosed with dentigerous cysts (DC) after obtaining the informed consent and the cystic fluid was subjected to biochemical analysis. RESULTS: Majority of the affected patients with DC were in their second decade and showed more predilection for mandible with a male predominance. The area of predilection was third molar region in the mandible and it is the canine region in maxilla. All the cases were associated with impacted teeth and majority showed expansion of the buccal/labial cortical plate. The various biochemical variables (total protein content, albumin, globulin and albumin: globulin ratio) were also assessed in the present study. CONCLUSION: The awareness of protean features of DC evident through this study is essential for the general as well as specialty practitioners for the accurate diagnosis and proper treatment planning of these non cancerous but potentially destructive lesions and also opens new avenues for further research.

Monostotic fibrous dysplasia with Raynaud's phenomenon.

Fibrous dysplasia (FD) is a benign bone disorder characterized by alteration in bone morphology. Monostotic FD is the commonest variant and affects the craniofacial bones. Raynaud's phenomenon is recurrent vasospasm of the fingers and toes due to cold exposure. The disease is usually idiopathic or secondary to connective tissue disorders. Raynaud's phenomenon is not described previously with FD. We recently encountered two interesting patients of craniofacial monostotic FD with Raynaud's phenomenon and report the same in this report.

Prevalence of oral submucous fibrosis among habitual gutkha and areca nut chewers in Moradabad district.

BACKGROUND: To determine the prevalence and severity of oral submucous fibrosis (OSMF) among habitual gutkha, areca nut and pan chewers of Moradabad, India. METHOD: A survey was conducted for a period of one year in east, west, north and south zones of Moradabad district, Uttar Pradesh. One thousand habitual chewers were selected as study participants, using a stratified random sampling technique, between the ages of 11-40 yrs, with a habit of chewing gutkha, areca nut, pan for over a year. A detailed history was recorded and meticulous clinical examination was conducted. Evaluation of taste sensation, hearing, interincisal distance, clinical staging was done in the OSMF patients found amongst habitual chewers. The obtained data was statistically analyzed using an SPSS 16.5 version soft ware. RESULTS: The prevalence of OSMF was 6.3% (63/1000) and gutkha chewing was the most common abusive habit (42/63) amongst OSMF patients. Stage 1, Stage 2, Stage 3 OSMF was seen in 28, 19 and 16 patients respectively. Restricted mouth opening, altered taste perception and defective hearing was observed in 37/63 (58.7%), 24/63 (38.09%) and 14/63 (22.22%) respectively. CONCLUSION: Our study shows a prevalence of 6.3% OSMF among habitual chewers of Moradabad. Prevalence and severity were more in urban and rural patients respectively.

Comparison of curcumin with intralesional steroid injections in Oral Submucous Fibrosis - A randomized, open-label interventional study.

INTRODUCTION: Oral Submucous Fibrosis (OSMF) is precancerous condition caused by areca nut chewing characterized by restricted mouth opening, burning sensation and stiffness & blanching of oral mucosa. Complete regression of the condition had not been achieved in all cases with any of the present treatment regimens. Curcumin is (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. Hence an interventional study was undertaken to establish the efficacy of curcumin in OSMF patients. SETTINGS & DESIGN: A randomized open label, interventional study was conducted in forty patients with clinically and histologically proven Oral Submucous Fibrosis. MATERIALS & METHODS: Forty patients with clinically and histologically proven Oral Submucous Fibrosis were selected for the study and were randomly divided into 2 groups. The first group was treated with weekly intralesional injection of 4 mg Dexamethasone & 1500 I.U Hyaluronidase and the second group by oral administration of two Curcumin tablets (Turmix 300 mg) per day for 3 months each. Improvement of burning sensation, interincisal distance and tongue protrusion was evaluated on a weekly basis. RESULTS: Burning sensation improved in both the groups from early to late stages. Complete resolution of burning sensation was noted with turmix. The mean increase in interincisal distance was 3.13 mm and 1.25 mm respectively in groups 1 &2. The interincisal distance improved in both the groups, with significant results at the end of first month. Tongue protrusion showed greater recovery at the end of 1st month in group 1 when compared with group 2. CONCLUSION: Turmix is beneficial and effective in reducing burning sensation in early OSMF patients.

The readability of editorials in popular Indian medical journals.

INTRODUCTION: The essence of communication is to convey a message, and readability tests have been developed to quantify this aspect of language. There is limited research on the readability tests of journal contents from India. In this study, we performed readability tests on the editorials of four popular Indian medical journals. MATERIALS AND METHODS: THE READABILITY TESTS (FLESCH SCORE, FLESCH GRADE, AND TEXT STATISTICS) WERE CALCULATED FROM THE FOLLOWING JOURNALS: Indian Journal of Endocrinology and Metabolism (IJEM), Journal of Association of Physicians of India (JAPI), Journal of Indian Medical Association (JIMA), and International Journal of Diabetes in Developing Countries (IJDDC). The editorials published in these journals over the last 2 tears were included in this analysis. RESULTS: A total of 64 editorials (IJEM - 19, JAPI - 18, JIMA - 16, IJDDC - 11) were analyzed in this study. The mean readability score was (IJEM 34.8 ± 9.5; JAPI 31.4 ± 11.4; JIMA 29.6 ± 10.1; IJDDC 26.1 ± 17.7) not different between the journals (P = 0.2666). Flesch score was less variable in IJEM an d JIMA than in JAPI and IJDDC (P = 0.0167). The editorials from IJEM and JAPI had a lower Flesch grade than the remaining two journals (P = 0.0253). The readability score was directly proportional to the sentence count and inversely proportional to the words per sentence (P < 0.0001). CONCLUSION: Our results suggest that the editorials from all the medical journals have equal readability scores. The sentence count and words per sentence are important to achieve a high readability score while writing for a journal.

Comparison of research productivity between metro and non-metro cities in a biomedical journal from India.

BACKGROUND: The research productivity of a place depends on doctors, patients and available infrastructure to carry research activities. AIMS: We aimed to study the publishing trends and research productivity of metro and non-metro cities in the Journal of the Association of Physi cians of India (JAPI). MATERIALS AND METHODS: Bibliometric analysis of research articles published in JAPI between 2000 and 2011was undertaken. The four types of articles (original articles including brief reports, case reports, correspondence and pictorial image) were studied for research productivity. They were analyzed according to subspecialty, publication times and type of research work from both places. Comparison between groups was done using Fisher exact and Mann-Whitney U test. Descriptive statistics were used and a P < 0.05 was considered significant. RESULTS: Of a total of 2977 articles, 1798 were available for analysis. Metros published 46% (825/1798) and non-metros 54% (973/1798). Original articles and case reports constituted 3/4(th) of the published literature from both places. Pictorial images were seen more from non-metro cities (P = 0.03). Mumbai and Delhi were leading from the metros, whereas Varanasi and Chandigarh were leading from the non-metro places. Endocrinology, Neurology, Cardiology and Infectious Diseases constituted the top four subspecialties from both places. Neurology articles were published more from non-metros (P = 0.03). The timelines from submission to publication varied between 12 and 15 months, and were lesser for articles from the metros (P = 0.01). CONCLUSIONS: Metros and non-metro cities are comparable in publishing trends and research productivity. Places with post-graduate institutes contribute majority of the research articles. Faster publication timelines from metros indicate better manuscript content and preparation.

Two interesting cases of EEC syndrome.

AIM: To report two cases of EEC syndrome with oral involvement to highlight the fact that the dental surgeon may be among the first to recognise the condition. INTRODUCTION: The EEC syndrome, a rare congenital syndrome is characterised by ectodermal dysplasia, distal limb anomaly, cleft lip and palate and lachrymal duct anomalies although the term oligosymptomatic EEC syndrome has been suggested for cases in which ectrodactyly may be absent and that such cases should not be deprived of the EEC syndrome diagnosis. It is usually inherited as an autosomal dominant trait with variable expressivity and penetrance and all these features rarely coexist in a single individual. CONCLUSION: Both our cases had all three characteristic features of the EEC syndrome. Other syndromes with overlapping features such as the Rapp-Hodgkin syndrome and the AEC syndrome should be considered in the differential diagnosis of incomplete forms of EEC syndrome. CLINICAL SIGNIFICANCE: It is important to follow an interdisciplinary approach to attain the greatest degree of success possible in the treatment of such cases.

Publication trends of research articles from infectious diseases specialty in a medical journal from India.

BACKGROUND: Details about research productivity in the infectious diseases specialty from India are lacking. OBJECTIVE: To analyse publishing trends and research productivity of articles related to infectious diseases in the Journal of the Association of Physicians of India (JAPI). MATERIALS AND METHODS: We carried out bibliometric analysis of articles related to infectious diseases specialty from JAPI published between 2000 and 2011. Data were derived from the journal's website and the articles were analysed for type (original article, case reports, etc.), microorganism (bacterial, viral, etc.) place of the research and timelines for publication. RESULTS: Out of 2977 articles published in JAPI over last 12 years, 256 articles belong to infectious diseases subspecialty. Infectious diseases contributed 11-18% of the published articles per year in JAPI during the last decade. Original articles (31%), case reports (38%) and correspondence (22%) constitute the majority of article types, while remaining 9% was made up by images. Bacterial (22%), protozoal and helminthic (20%), HIV (15%) and mycobacterial (16%) diseases lead the type of microorganisms represented in the research articles. Mumbai (16%), Delhi (9%) and Kolkata (7%) are the top three places contributing to the articles, followed by Chandigarh and Chennai. Original articles and case reports took approximately 14 months for publication, as compared to 6 months for an image (P < 0.0001). CONCLUSION: Infectious diseases specialty contributes about 15% of articles per annum in JAPI. HIV and tuberculosis together account for 30% of published literature with fair representation from other organisms. Mumbai and Delhi are the leading contributors towards research productivity in this specialty.

Publication trends of neurology articles in a biomedical journal from India.

BACKGROUND: The details about the research productivity in the neurology specialty from India is lacking. We analyzed the publishing trends and the research productivity of neurology-related articles in the Journal of the Association of Physicians of India (JAPI). MATERIALS AND METHODS: We carried the bibliometric analysis of articles related to neurology specialty from JAPI published between 2000 and 2011. Data were derived from the journal's website and the articles were analyzed for type (original article, case reports, etc.), disease (infection, vascular, etc.), place, and timelines for publication. RESULTS: Out of total 2977 articles published, 256 articles belong to neurology. Neurology contributed to 7--20% of the published articles per year in JAPI. Case reports (52%) constitute the majority type of articles followed by Original Articles (20%), Correspondence and Images (15% each). Infections (27%), structural disorders (19%), cerebrovascular and peripheral nervous system disorders (16% each) contribute the majority of research articles in Neurology. Mumbai (15%), Delhi (13%), and Chennai (9%) are the top three contributors followed by Lucknow and Varanasi. All types of articles took about 9--10 months for acceptance and another 4--5 months for publication. Letters to the Editor were published faster when compared to other articles (P=0.0035). CONCLUSION: Neurology specialty contributes an average 14% of articles per annum in JAPI. Infections, vascular, structural, and peripheral nervous system disorders together account for 80% of published literature with a small representation from other diseases. Mumbai and Delhi are the leading contributors toward research productivity in neurology.