The Use of Glenoid Structural Allografts for Glenoid Bone Defects in Reverse Shoulder Arthroplasty.

Background: The use of reverse shoulder arthroplasty as a primary and revision implant is increasing. Advances in implant design and preoperative surgical planning allow the management of complex glenoid defects. As the demand for treating severe bone loss increases, custom allograft composites are needed to match the premorbid anatomy. Baseplate composite structural allografts are used in patients with eccentric and centric defects to restore the glenoid joint line. Preserving bone stock is important in younger patients where a revision surgery is expected. The aim of this article is to present the assessment, planning, and indications of femoral head allografting for bony defects of the glenoid. Methods: The preoperative surgical planning and the surgical technique to execute the plan with a baseplate composite graft are detailed. The preliminary clinical and radiological results of 29 shoulders which have undergone this graft planning and surgical technique are discussed. Clinical outcomes included visual analogue score of pain (VAS), American Shoulder and Elbow Surgeons score (ASES), Constant-Murley score (CS), satisfaction before and after operation, and active range of motion. Radiological outcomes included graft healing and presence of osteolysis or loosening. Results: The use of composite grafts in this series has shown excellent clinical outcomes, with an overall graft complication rate in complex bone loss cases of 8%. Conclusion: Femoral head structural allografting is a valid and viable surgical option for glenoid bone defects in reverse shoulder arthroplasty.

Assessment of the Knowledge, Attitudes, and Practices of Indian Medical Students Towards Coronavirus Disease 2019 (COVID-19) After Two Doses of Vaccination and Their Approach Towards the Third (Booster) Dose.

Background and objectives Medical students not only directly impact coronavirus disease 2019 (COVID-19) transmission due to their behavior and perceptions but also play an important role in influencing the behavior and vaccine intentions of their families and the community at large. The study's objective was to assess the knowledge, attitudes, and practices of medical students who have completed two doses of the COVID-19 vaccine towards the disease and their approach towards the third (booster) dose. Methods A total of 705 individual responses were obtained from a cross-sectional web-based study deployed using Google Forms. After getting consent and basic information, data was obtained regarding knowledge of the disease, attitudes towards the disease, and practices regarding the same. The mean score was calculated for the above different categories and compared with their respective cut-offs using a one-sample t-test. Data was also collected regarding their approach towards the booster dose of the COVID-19 vaccine, and the proportion of each response for different categories of questions was calculated. Results Participants were found to have mean scores in the range of moderate knowledge in the first part (47.67±4.49) and the second part (6.96±1.10) of the questionnaire and moderate practices (30.6±4.27) regarding COVID-19 disease. However, they had a mean score in the range of low attitude (39.79±4.07). The majority of participants acknowledge the role of vaccines in preventing the severity and spread of the disease (71.95%) and its effect on workers and medical professionals (60.26%). Mixed opinions were obtained for concerns regarding its pre-market testing and adverse effects and the government's vaccination policy. Interpretation and conclusion Responses of the medical students obtained in this study were majorly positive and in accordance with pre-vaccination studies concerning knowledge and practices. However, the low mean score in attitude obtained can be possibly explained due to their lack of direct exposure to patient management during the pandemic. The majority of participants had a positive response towards the use of the vaccine and the effectiveness of the booster dose, but concerns regarding pre-market testing, adverse effects, and the government's vaccination policy suggested the role of awareness campaigns and government endeavors to curb the same.

All-arthroscopic supraspinatus and infraspinatus muscle advancement leads to high healing rate and excellent outcomes in patients with massive, retracted rotator cuff tears, even in patients with pseudoparalysis.

PURPOSE: The purpose of this study was to evaluate the clinical and radiographic outcomes of an all-arthroscopic rotator cuff repair technique involving muscle advancement and double-layer lasso loop (DLLL) repair for massive, retracted posterosuperior cuff tears. METHODS: This is a retrospective case series of patients with massive, retracted posterosuperior cuff tears who underwent the all-arthroscopic muscle advancement technique from March 2017 to September 2021, with minimum follow-up of 12 months. Key steps included suprascapular nerve release, advancement of supraspinatus and infraspinatus muscles, and DLLL repair. Preoperative and postoperative visual analogue scale for pain, American Shoulder and Elbow Surgeons (ASES) score, Constant score, University of California Los Angeles (UCLA) shoulder score, active range of motion (ROM), and strength were compared. Preoperative and postoperative structural radiological characteristics were analysed. RESULTS: Forty-three shoulders in 38 patients were evaluated with mean follow-up of 18.8 months (range 12-55 months). Of the 43 shoulders, 4 repairs failed (9.3% retear rate). VAS, ASES, Constant, and UCLA scores significantly improved (p<0.001) in patients who demonstrated healing on postoperative MRI (n=39). ASES, Constant, and UCLA scores were significantly better in the healed group, with 100% exceeding MCIDs for ASES and UCLA scores, and 84.2% for Constant score. A lower proportion of patients in the retear group achieved MCIDs. Active ROM in all planes significantly improved for those who had healed repairs. (p<0.001). Relative strengths of abduction, supraspinatus, and infraspinatus were at least 90% of the contralateral side. Recovery rate of pseudoparalysis (7 patients) was 100%. CONCLUSION: All-arthroscopic muscle advancement, coupled with double-layer lasso loop repair, leads to a high healing rate with excellent clinical outcomes and recovery of strength to at least 90%, even in patients with pseudoparalysis.

Development and validation of a preliminary multivariable diagnostic model for identifying unusual infections in hospitalized patients.

Diagnostic delay leads to poor outcomes in infections, and it occurs more often when the causative agent is unusual. Delays are attributable to failing to consider such diagnoses in a timely fashion. Using routinely collected electronic health record (EHR) data, we built a preliminary multivariable diagnostic model for early identification of unusual fungal infections and tuberculosis in hospitalized patients. We conducted a two-gate case-control study. Cases encompassed adult patients admitted to 19 Mayo Clinic enterprise hospitals between January 2010 and March 2023 diagnosed with blastomycosis, cryptococcosis, histoplasmosis, mucormycosis, pneumocystosis, or tuberculosis. Control groups were drawn from all admitted patients (random controls) and those with community-acquired infections (ID-controls). Development and validation datasets were created using randomization for dividing cases and controls (7:3), with a secondary validation using ID-controls. A logistic regression model was constructed using baseline and laboratory variables, with the unusual infections of interest outcome. The derivation dataset comprised 1043 cases and 7000 random controls, while the 451 cases were compared to 3000 random controls and 1990 ID-controls for validation. Within the derivation dataset, the model achieved an area under the curve (AUC) of 0.88 (95% confidence interval [CI]: 0.87-0.89) with a good calibration accuracy (Hosmer-Lemeshow P = 0.623). Comparable performance was observed in the primary (AUC = 0.88; 95% CI: 0.86-0.9) and secondary validation datasets (AUC = 0.84; 95% CI: 0.82-0.86). In this multicenter study, an EHR-based preliminary diagnostic model accurately identified five unusual fungal infections and tuberculosis in hospitalized patients. With further validation, this model could help decrease time to diagnosis.

En bloc resection followed by gluteal advancement flap for sacral Ewing's sarcoma: A novel technique.

Ewing's sarcoma is a rare and highly aggressive bone tumor primarily affecting children and adolescents. It commonly presents in the pelvic and axial skeleton, with sacral involvement posing unique challenges due to its intricate anatomical location. This report details the case of an 18-year-old male with sacral Ewing's sarcoma, emphasizing the diagnostic, surgical, and reconstructive aspects of management. The patient presented with lower back pain, lower limb weakness, and urinary incontinence, which prompted an extensive diagnostic evaluation. Magnetic resonance imaging and computed tomography scans revealed a large lytic mass extending from the S2 vertebra to the coccyx invading the presacral space. Biopsy confirmed the diagnosis of Ewing's sarcoma, characterized by the EWS-FLI1 type 1 translocation. A multidisciplinary team comprising neurosurgeons, colorectal surgeons, and plastic surgeons was formulated. En bloc resection of the tumor, lumbopelvic fixation, and soft-tissue reconstruction using bilateral gluteus maximus advancement flaps were successfully performed. The procedure aimed to address both the oncological and functional aspects of the patient's condition. Chemotherapy and radiotherapy were administered as adjuvant therapies. At 2-year follow-up, the patient was ambulating independently with no residual tumor on imaging. This case highlights the complex nature of sacral Ewing's sarcoma and underscores the importance of a multidisciplinary approach. The described surgical technique, including the innovative use of gluteus maximus advancement flaps for soft-tissue reconstruction, contributes to reducing wound complications and promoting successful patient outcomes. The presented approach serves as a valuable addition to the armamentarium of treatment options for this challenging malignancy.

Creation of Multi-Principal Element Alloy NiCoCr Nanostructures via Nanosecond Laser-Induced Dewetting.

The multi-principal element alloy nanoparticles (MPEA NPs), a new class of nanomaterials, present a highly rewarding opportunity to explore new or vastly different functional properties than the traditional mono/bi/multimetallic nanostructures due to their unique characteristics of atomic-level homogeneous mixing of constituent elements in the nanoconfinements. Here, the successful creation of NiCoCr nanoparticles, a well-known MPEA system is reported, using ultrafast nanosecond laser-induced dewetting of alloy thin films. Nanoparticle formation occurs by spontaneously breaking the energetically unstable thin films in a melt state under laser-induced hydrodynamic instability and subsequently accumulating in a droplet shape via surface energy minimization. While NiCoCr alloy shows a stark contrast in physical properties compared to individual metallic constituents, i.e., Ni, Co, and Cr, yet the transient nature of the laser-driven process facilitates a homogeneous distribution of the constituents (Ni, Co, and Cr) in the nanoparticles. Using high-resolution chemical analysis and scanning nanodiffraction, the environmental stability and grain arrangement in the nanoparticles are further investigated. Thermal transport simulations reveal that the ultrashort (≈100 ns) melt-state lifetime of NiCoCr during the dewetting event helps retain the constituent elements in a single-phase solid solution with homogenous distribution and opens the pathway to create the unique MPEA nanoparticles with laser-induced dewetting process.

Natural history of craniovertebral abnormalities in a single-center study in 54 patients with Hurler syndrome.

OBJECTIVE: Craniovertebral junction (CVJ) abnormalities are common and well documented in mucopolysaccharidosis type I-Hurler syndrome (MPS IH), often causing severe spinal canal narrowing. However, the requirement for surgical decompression and/or fusion is uncommon. Although hematopoietic cell transplant (HCT) has been shown to prolong the lives of patients with MPS IH, its effect in halting or reversing musculoskeletal abnormalities is less clear. Unfortunately, there are currently no universal guidelines for imaging or indication for surgical interventions in these patients. The goal of this study was to track the progression of the CVJ anatomy in patients with MPS IH following HCT, and to examine radiographic features in patients who needed surgical intervention. METHODS: Patients with MPS IH treated at the University of Minnesota with allogeneic HCT between 2008 and 2020 were retrospectively reviewed. Patients who underwent CVJ surgery were identified with chart review. All MPS IH cervical scans were examined, and the odontoid retroflexion angle, clivoaxial angle (CXA), canal width, and Grabb-Oakes distance (pB-C2) were measured yearly for up to 7 years after HCT. Longitudinal models based on the measurements were made. An intraclass correlation coefficient was used to measure interrater reliability. Nine children without MPS IH were examined for control CVJ measurements. RESULTS: A total of 253 cervical spine MRI scans were reviewed in 54 patients with MPS IH. Only 4 (7.4%) patients in the study cohort required surgery. Three of them had posterior fossa and C1 decompression, and 1 had a C1-2 fusion. There was no statistically significant difference in the spinal parameters that were examined between surgery and nonsurgery groups. Among the measurements, canal width and CXA varied drastically in patients with different neck positions. Odontoid retroflexion angle and CXA tended to decrease with age. Canal width and pB-C2 tended to increase with age. CONCLUSIONS: Based on the data, the authors observed an increase in canal width and pB-C2, whereas the CXA and odontoid retroflexion angle became more acute as the patients aged after HCT. The longitudinal models derived from these data mirrored the development in children without MPS IH. Spinal measurements obtained on MR images alone are not sufficient in identifying patients who require surgical intervention. Symptom monitoring and clinical examination, as well as pathological spinal cord changes on MRI, are more crucial in assessing the need for surgery than is obtaining serial imaging.

Time-elapsed microstructural imaging of failure of the reverse shoulder implant.

BACKGROUND: Reverse Shoulder Arthroplasties (RSA) have become a primary choice for improving shoulder function and pain. However, the biomechanical failure mechanism of the humeral component is still unclear. The present study reports a novel protocol for microstructural imaging of the entire humerus implant under load before and after fracture. METHODS: A humerus specimen was obtained from a 75-year-old male donor. An expert surgeon implanted the specimen with a commonly used RSA implant (Aequalis reversed II, Stryker Orthopaedics, USA) and surgical procedure. The physiological glenohumeral contact force that maximized the distal implant migration was selected from a public repository ( orthoload.com ). Imaging and concomitant mechanical testing were performed using a large-volume micro-CT scanner (Nikon XT H 225 ST) and a custom-made compressive stage. Both when intact and once implanted, the specimen was tested under a pre-load and by imposing a constant deformation causing a physiological reaction load (650 N, 10 degrees adducted). The deformation of the implanted specimen was then increased up to fracture, which was identified by a sudden drop of the reaction force, and the specimen was then re-scanned. RESULTS: The specimen's stiffness decreased from 874 N/mm to 464 N/mm after implantation, producing movements of the bone-implant interface consistent with the implant's long-term stability reported in the literature. The micro-CT images displayed fracture of the tuberosity, caused by a combined compression and circumferential tension, induced by the distal migration of the implant. CONCLUSION: The developed protocol offers detailed information on implant mechanics under load relative to intact conditions and fracture, providing insights into the failure mechanics of RSA implants. This protocol can be used to inform future implant design and surgical technique improvements.

Trustworthy deep learning framework for the detection of abnormalities in X-ray shoulder images.

Musculoskeletal conditions affect an estimated 1.7 billion people worldwide, causing intense pain and disability. These conditions lead to 30 million emergency room visits yearly, and the numbers are only increasing. However, diagnosing musculoskeletal issues can be challenging, especially in emergencies where quick decisions are necessary. Deep learning (DL) has shown promise in various medical applications. However, previous methods had poor performance and a lack of transparency in detecting shoulder abnormalities on X-ray images due to a lack of training data and better representation of features. This often resulted in overfitting, poor generalisation, and potential bias in decision-making. To address these issues, a new trustworthy DL framework has been proposed to detect shoulder abnormalities (such as fractures, deformities, and arthritis) using X-ray images. The framework consists of two parts: same-domain transfer learning (TL) to mitigate imageNet mismatch and feature fusion to reduce error rates and improve trust in the final result. Same-domain TL involves training pre-trained models on a large number of labelled X-ray images from various body parts and fine-tuning them on the target dataset of shoulder X-ray images. Feature fusion combines the extracted features with seven DL models to train several ML classifiers. The proposed framework achieved an excellent accuracy rate of 99.2%, F1Score of 99.2%, and Cohen's kappa of 98.5%. Furthermore, the accuracy of the results was validated using three visualisation tools, including gradient-based class activation heat map (Grad CAM), activation visualisation, and locally interpretable model-independent explanations (LIME). The proposed framework outperformed previous DL methods and three orthopaedic surgeons invited to classify the test set, who obtained an average accuracy of 79.1%. The proposed framework has proven effective and robust, improving generalisation and increasing trust in the final results.

Analysis of Cutaneous Adverse Drug Reactions (ADR) Reported at an ADR Monitoring Center of a Tertiary Care Teaching Institute in Central India.

Background Cutaneous adverse drug reactions (ADRs) are among the most frequent ADRs. Knowledge of the pattern of cutaneous ADRs (CADRs) and causal drugs helps prevent and reduce the incidence of CADR, which in turn reduces the incidence of hospitalization and expenses for the patient. Objectives To analyze CADR according to demographic profile, morphological pattern, causative drugs, severity, and outcome in patients suffering from CADRs. Materials and methods Retrospective data analysis was conducted in the Adverse Drug Reaction Monitoring Centre (AMC) of the tertiary care teaching institute between February 2020 and September 2023 under the Pharmacovigilance Program of India (PvPI). All ADRs reported were analyzed based on the following parameters: total number of ADRs reported, number of CADRs, information related to demographic parameters, the clinical presentation of CADRs, and suspected medication. Causality assessment was done using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) scale. Severity was assessed using a modified Hartwig and Seigel scale. Results A total of 125 CADRs were analyzed. Considering the gender-wise distribution, 65 females and 60 males suffered from CADR. The most common drug category responsible for CADRs was antimicrobials (63.2%), followed by topical agents (12.8%). Maculopapular rash (33.6%) was the most common presenting symptom, followed by itching (27.2%). Few patients suffered from serious CADRs such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).  Conclusion A wide clinical spectrum of CADRs ranging from maculopapular rash to fixed-drug eruption to serious SJS was observed in our study. The most common causative agents for CADRs were antimicrobials, followed by topical agents and NSAIDs. For early diagnosis and management of CADRs, it is critical to have data on the potential cutaneous adverse effects of commonly used drugs, to educate the patients regarding common early symptoms of drug reactions (e.g., erythematous rash, edema, urticaria, mucosal erosions, itching, burning of skin, etc.), and to monitor the patient, especially during the start of therapy. To ease the burden of CADRs, a therapeutic plan of anticipating, avoiding, recognizing, and responding to ADRs should be implemented.

Impact of short-term application of continuous glucose monitoring system(CGMS) on long-term glycemic profile in adolescents and adults with type 1 diabetes mellitus: An open-label randomized control cross over study.

AIMS: The use of Continuous Glucose Monitoring System (CGMS) improves glycemic parameters in Type 1 Diabetes Mellitus (T1D), but the cost is prohibitive. Here, we investigated the effect of short-term application of real-time and intermittently-scanned CGMS (rt and is-CGMS) in T1D individuals on change in HbA1c at the end of 3 months. METHODS: T1D individuals were randomized into three groups in a ratio of 1:1:2 - Group A (rt-CGMS for 2 weeks initially, followed by is-CGMS for 2 weeks at 3 months), Group B (is-CGMS for 2 weeks initially followed by rt-CGMS for 2 weeks at 3 months) and Group C (only self-monitoring of blood glucose), respectively. HbA1c at baseline, 3, and 6 months were compared. RESULTS: Out of a total 68 T1D patients, HbA1c decreased significantly in groups A and B at 6 months compared to the baseline, but not in group C. HbA1c was significantly lower in Group A compared to Group C at 3 and 6 months. Fructosamine levels significantly decreased in Group B before and after cross-over. Glycemic variability indices improved significantly after cross-over from is-CGMS to rt-CGMS. CONCLUSION: Intermittent application of CGMS for 2 weeks improves short- and long-term blood glucose control in T1D.

Topical antibiotics in the prevention of port-site infection after elective day care laparoscopic cholecystectomy.

BACKGROUND: Wound-related infections and complications are rare after day care laparoscopic cholecystectomy (LC). They can have a significant adverse impact on the postoperative course after an uneventful elective LC. The use of topical antibiotics over the port site may prevent such complications. MATERIALS AND METHODS: This trial was conducted from January 2018 to June 2019. Two hundred and fifty patients who met the inclusion and exclusion criteria were included in the study. They were randomized into the topical antibiotic group (Group A, n = 125) and control group (Group B, n = 125). All patients underwent four-port LC. Mupirocin 2% topical antibiotic ointment was applied to all four-port sites in Group A, whereas no topical antibiotic was used in Group B. One dose of prophylactic systemic antibiotics was given to all patients in both groups. RESULTS: The mean age was 43.22 ± 12.7 years in Group A and 43.44 ± 12.5 years in Group B. The comorbidities and the other variables were comparable between the two groups. The port-site infection (PSI) was observed in one patient in Group A and three patients in Group B, which was statistically nonsignificant (P = 0.622). The mean time of detection of infection was 4.75 ± 1.7 days. All the infections were superficial surgical site infections. Microbiological swabs culture of the infected wounds yielded no growth of bacteria. CONCLUSION: The PSI after LC is very less. The use of topical antibiotics to prevent PSIs after LC could not be established.

Single-access, non-contrast transcatheter aortic valve implantation, the ultimate minimalist approach: a case report.

Background: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with symptomatic severe aortic stenosis. Patients with previous renal transplant are considered as a high-risk cohort who may develop procedural complications related to vascular access and renal impairment post-TAVI. Case summary: Herein, we report a case of an 88-year-old male who presented with progressive dyspnoea. His transthoracic echocardiogram revealed severe aortic stenosis with a peak gradient of 75 mmHg and impaired left ventricle systolic function (an estimated ejection fraction of 40%). He had a background of kidney transplant with progressive decline in renal function, requiring the formation of left arm arteriovenous fistula in preparation for future dialysis. He was successfully treated with TAVI using a single vascular access site without administering contrast media. Discussion: Single-access, non-contrast TAVI is feasible when treating renal transplant patients with severe aortic stenosis and limited vascular access. The current minimalistic approach should be used only in highly selective patient cases.

Clinical Outcomes of ULTRA EZY Bar vs Erich Arch Bar in Conservative Management of Maxillofacial Fractures: A Randomized Controlled Trial.

Objective: Various techniques have been employed from time to time to achieve maxillomandibular fixation, and arch bars provide an effective and versatile means of maxillomandibular fixation, and however, some of the issues occurring with it have been eliminated with the introduction of Ultralock EZY bar. The aim of the present study is to compare the advantages and disadvantages of Ultralock Ezy bar over the Erich arch bar in mid-face fracture or maxillary fracture or mandibular fracture or both requiring conservative treatment. Materials and Methods: A total of 20 patients reported to the Department of Oral and Maxillofacial Surgery in Sudha Rustagi Dental College and Hospital, Faridabad, with mid-face fracture/maxillary fracture, mandibular fracture or both. The treatment plan required intermaxillary fixation. As a part of treatment plan, group was selected randomly divided into 20 arches in each group that is test arch group and control arch group.Test arch group included arches in which Ultralock EZY bar was done. Control arch group included arches in which Erich arch bar was done. The parameters compared in both the groups were surgical time taken, injuries due to wires, arch bar stability, oral hygiene index, patient acceptance and comfort, pulp vitality, and complication (if any). Results: The average surgical time taken was less, and oral hygiene status and patient acceptance were better in test group. There was not much statistically significant difference in pulp vitality but number of cases with absence of pulp vitality were more in test group. Conclusion: This study emphasizes the use of Ultralock Ezy bar as a quick and easy method than Erich arch bar. Oral hygiene maintenance was comparatively better in patients with Ultralock Ezy bar than those with Erich arch bar. For the patients who require long-term IMF, Ultralock Ezy bars can be a viable option. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-022-01821-3.

Identification of potent BRD4-BD1 inhibitors using classical and steered molecular dynamics based free energy analysis.

In the present work a combination of traditional and steered molecular dynamics based techniques were employed to identify potential inhibitors against the human BRD4 protein (BRD4- BD1); an established drug target for multiple illnesses including various malignancies. Quinoline derivatives that were synthesized in-house were tested for their potential as new BRD4-BD1 inhibitors. Initially molecular docking experiments were performed to determine the binding poses of BRD4-BD1 inhibitors. To learn more about the thermodynamics of inhibitor binding to the BRD4-BD1 active site, the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) free energy calculations were conducted afterwards. The findings of the MM-PBSA analysis were further reinforced by performing steered umbrella sampling simulations which revealed crucial details about the binding/unbinding process of the most potent quinoline derivatives at the BRD4-BD1 active site. We report a novel quinoline derivative which can be developed into a fully functional BRD4-BD1 inhibitor after experimental validation. The identified compound (4 g) shows better properties than the standard BRD4-BD1 inhibitors considered in the study. The study also highlights the crucial role of Gln78, Phe79, Trp81, Pro82, Phe83, Gln84, Gln85, Val87, Leu92, Leu94, Tyr97, Met105, Cys136, Asn140, Ile146 and Met149 in inhibitor binding. The study provides a possible lead candidate and key amino acids involved in inhibitor recognition and binding at the active site of BRD4-BD1 protein. The findings might be of significance to medicinal chemists involved in the development of potent BRD4-BD1 inhibitors.

Identification, characterization, and CADD analysis of Plasmodium DMAP1 reveals it as a potential molecular target for new anti-malarial discovery.

Developing drug resistance in the malaria parasite is a reason for apprehension compelling the scientific community to focus on identifying new molecular targets that can be exploited for developing new anti-malarial compounds. Despite the availability of the Plasmodium genome, many protein-coding genes in Plasmodium are still not characterized or very less information is available about their functions. DMAP1 protein is known to be essential for growth and plays an important role in maintaining genomic integrity and transcriptional repression in vertebrate organisms. In this study, we have identified a homolog of DMAP1 in P. falciparum. Our sequence and structural analysis showed that although PfDMAP1 possesses a conserved SANT domain, parasite protein displays significant structural dissimilarities from human homolog at full-length protein level as well as within its SANT domain. PPIN analysis of PfDMAP1 revealed it to be vital for parasite and virtual High-throughput screening of various pharmacophore libraries using BIOVIA platform-identified compounds that pass ADMET profiling and showed specific binding with PfDMAP1. Based on MD simulations and protein-ligand interaction studies two best hits were identified that could be novel potent inhibitors of PfDMAP1 protein.Communicated by Ramaswamy H. Sarma.

Comparison of Shoulder Range of Motion Quantified with Mobile Phone Video-Based Skeletal Tracking and 3D Motion Capture-Preliminary Study.

BACKGROUND: The accuracy of human pose tracking using smartphone camera (2D-pose) to quantify shoulder range of motion (RoM) is not determined. METHODS: Twenty healthy individuals were recruited and performed shoulder abduction, adduction, flexion, or extension, captured simultaneously using a smartphone-based human pose estimation algorithm (Apple's vision framework) and using a skin marker-based 3D motion capture system. Validity was assessed by comparing the 2D-pose outcomes against a well-established 3D motion capture protocol. In addition, the impact of iPhone positioning was investigated using three smartphones in multiple vertical and horizontal positions. The relationship and validity were analysed using linear mixed models and Bland-Altman analysis. RESULTS: We found that 2D-pose-based shoulder RoM was consistent with 3D motion capture (linear mixed model: R2 > 0.93) but was somewhat overestimated by the smartphone. Differences were dependent on shoulder movement type and RoM amplitude, with adduction the worst performer among all tested movements. All motion types were described using linear equations. Correction methods are provided to correct potential out-of-plane shoulder movements. CONCLUSIONS: Shoulder RoM estimated using a smartphone camera is consistent with 3D motion-capture-derived RoM; however, differences between the systems were observed and are likely explained by differences in thoracic frame definitions.

Comparison of quantitative PCR and digital PCR assays for quantitative detection of infectious bronchitis virus (IBV) genome.

The quantitative polymerase chain reaction (qPCR) technique is an extensively used molecular tool for the detection and quantification of viral genome load. However, since the qPCR assay is a relative quantification method that relies on an external calibration curve it has a lower assay precision and sensitivity. The digital PCR (dPCR) technique is a good alternative to the qPCR assay as it offers highly precise and direct quantification of viral genome load in samples. In this study, performance characteristics such as the quantification range, sensitivity, precision, and specificity of the dPCR technique was compared to qPCR technique for the detection and quantification of IBV genome loads in serial dilutions of IBV positive plasmid DNA, and IBV infected chicken tissue and swab samples. The quantification range of the qPCR assay was wider than that of the dPCR assay, however dPCR had a higher sensitivity compared to qPCR. The precision of quantification of DNA in plasmid samples in terms of repeatability and reproducibility of results was higher when using the dPCR assay compared to qPCR assay. The quantification results of IBV genome load in infected samples by the qPCR and dPCR assays displayed a high correlation. Hence, our findings suggest that dPCR could be used in avian virology research for improved precision and sensitivity in detection and quantification of viral genome loads.

Richer than previously probed: An application of 1H NMR reveals one hundred metabolites using only fifty microliter serum.

The classical approach restricts the detection of metabolites in serum samples by using nuclear magnetic resonance (NMR) spectroscopy; however, the presence of copious proteins and lipoproteins emphasize and necessitate the development of a contemporary, high-throughput tactic. To eliminate the lipoproteins and proteins from sera to engender filtered sera (FS), the study was executed with 50 µl serum obtained from five healthy individuals with 5 years of age difference from 25 to 45 years old and the application of a unique mechanical filter with molecular weight cut-off value of 2KDa. The 10 µl FS from each individual was pooled to make 50 µl final volume filled in a co-axial tube for acquisition of a battery of 1D/2D investigations at 800 MHz NMR spectrometer and the assigned metabolites was confirmed through mass spectrometry as well as by comparing 1H NMR spectra of individual metabolites. This innovative tactic is commissioning to reveal more than 100 metabolites. In contrast to the protein precipitation method, 24 new metabolites were recognized in the present study. The present innovative approach characterizes nucleosides, nitrogenous bases, and volatile metabolites that possibly produce a landmark for the delineation of a comprehensive metabolic profile applicable for detection of the molecular cause of pathogenicity, early-stage disease detection and prognosis, inborn error of metabolism, and forensic investigations exerting the least volume of FS and NMR spectroscopy. The assignment of 100 metabolites using 1H NMR-based FS is described for the first time in the present report.

Age-related changes in geometry and transparency of human crystalline lens revealed by optical signal discontinuity zones in swept-source OCT images.

BACKGROUND: The shape and microstructure of the human crystalline lens alter with ageing, and this has an effect on the optical properties of the eye. The aim of this study was to characterise the age-related differences in the morphology and transparency of the eye lenses of healthy subjects through the optical signal discontinuity (OSD) zones in optical coherence tomography (OCT) images. We also investigated the association of those changes with the optical quality of the eye and visual function. METHODS: OCT images of the anterior segment of 49 eyes of subjects (9-78 years) were acquired, and the OSD zones (nucleus, C1-C4 cortical zones) were identified. Central thickness, curvature and optical density were measured. The eye's optical quality was evaluated by the objective scatter index (OSI). Contrast sensitivity and visual acuity tests were performed. The correlation between extracted parameters and age was assessed. RESULTS: The increase in lens thickness with age was dominated by the thickening of the cortical zone C3 (0.0146 mm/year). The curvature radii of the anterior lens surface and both anterior and posterior nucleo-cortical interfaces decreased with age (- 0.053 mm/year, - 0.013 mm/year and - 0.006 mm/year, respectively), and no change was observed for the posterior lens radius. OCT-based densitometry revealed significant correlations with age for all zones except for C1ß, and the highest increase in density was in the C2-C4 zones (R = 0.45, 0.74, 0.56, respectively, P < 0.001). Increase in OSI was associated with the degradation of visual function. CONCLUSIONS: OCT enables the identification of OSD zones of the crystalline lens. The most significant age-related changes occur in the C3 zone as it thickens with age at a faster rate and becomes more opaque than other OSD zones. The changes are associated with optical quality deterioration and reduction of visual performance. These findings contribute to a better understanding of the structure-function relationship of the ageing lens and offer insights into both pathological and aging alterations.