Titanium-Catalyzed Selective N-Alkylation of Amines with Alcohols via Borrowing Hydrogen Methodology.

The N-alkylation of amines with alcohols using earth-abundant and nonprecious metal catalysts has gained considerable attention in the pharmaceutical industry. We described titanium-catalyzed synthetic protocol for N-alkylation of amines with alcohols via borrowing hydrogen or hydrogen autotransfer reactions. The methodology enables the selective monoalkylation of various substituted (hetero)aromatic amines in good to excellent yields (up to 97% yield). The importance of the protocol was further demonstrated by the applicability of earth-abundant metal catalysis and the synthesis of 32 N-alkylated amines. The work allows the utilization of titanium-based catalysts for various reactions to expand the nature blueprint in catalysis.

Influence of three different fixation methods on femoral tunnel widening in ACL reconstructed patients evaluated using computed tomography (CT) scan.

PURPOSE: To evaluate femoral tunnel widening in young and active patients undergoing ACL reconstruction with quadrupled hamstring graft with fixation on tibial side performed with a Bioscrew while femoral fixation performed with either a Tight rope Reverse Threaded (RT) or Transfix or another Bioscrew using CT scan. MATERIAL AND METHOD: A total of 100 consecutive patients underwent single-bundle ACL reconstruction from January 2008 to March 2012. Eighty-six out of these were available with us till the final follow-up. Only 20-40-year-old males with unilateral ACL rupture less than a year old, diagnosed clinically and confirmed radiologically by magnetic resonance imaging, were selected for the study. All patients were evaluated clinically as well as radiologically at follow-up of 2 weeks, 1 month, 3 months, 6 months, 1 year and every 6 months thereafter. CT scans were performed at 2 weeks, 6 months, and 1 year postoperatively. The data acquired at the second week were considered as baseline data and were used for comparison with the data acquired at 6 months and 1 year. RESULTS: The dilatation at the aperture was significantly more in the Tight rope RT group as compared to the other two groups (p value 0.019 and 0.021 for sagittal and coronal images, respectively). CONCLUSION: There is no significant difference between the three different fixation modes in context of tunnel enlargement except with Tight rope RT device which leads to statistically significant dilatation at aperture. Future studies with longer follow-up are required to evaluate its clinical implications.

Proteomics in reproductive biology: beacon for unraveling the molecular complexities.

Proteomics, an interface of rapidly evolving advances in physics and biology, is rapidly developing and expanding its potential applications to molecular and cellular biology. Application of proteomics tools has contributed towards identification of relevant protein biomarkers that can potentially change the strategies for early diagnosis and treatment of several diseases. The emergence of powerful mass spectrometry-based proteomics technique has added a new dimension to the field of medical research in liver, heart diseases and certain forms of cancer. Most proteomics tools are also being used to study physiological and pathological events related to reproductive biology. There have been attempts to generate the proteomes of testes, sperm, seminal fluid, epididymis, oocyte, and endometrium from reproductive disease patients. Here, we have reviewed proteomics based investigations in humans over the last decade, which focus on delineating the mechanism underlying various reproductive events such as spermatogenesis, oogenesis, endometriosis, polycystic ovary syndrome, embryo development. The challenge is to harness new technologies like 2-DE, DIGE, MALDI-MS, SELDI-MS, MUDPIT, LC-MS etc., to a greater extent to develop widely applicable clinical tools in understanding molecular aspects of reproduction both in health and disease.

Reducing musculoskeletal disorders in iron ore mine operators: A fuzzy-based intervention approach.

BACKGROUND: This study focuses on evaluating the exposure to whole-body vibration (WBV) and association of musculoskeletal disorders (MSDs) with various risk factors among dumper operators in the mining industry. Despite the issue's significance, prior research has been limited. OBJECTIVE: The study introduces a novel fuzzy-based approach for identifying, selecting, and prioritizing safety measures to mitigate MSD risks. METHODS: Data collection comprised face-to-face interviews, anthropometric measurements, Rapid Upper Limb Assessment (RULA) scoring for posture assessment, and the Nordic Musculoskeletal questionnaire for assessment of MSD prevalence. Multiple linear and logistic regression models were used to analyse the contributing risk factors to MSDs and WBV exposure. These risk factors formed the basis for a practical approach to select appropriate safety measures based on fuzzy based aggregation method of expert's judgment aimed at mitigating the risk of MSDs. RESULTS: The results revealed that the risk factors such as poor work posture, WBV exposure and poor seat design were significantly associated with neck (adjusted odds ratio aOR = 4.81), upper limb and shoulder (aOR = 3.28), upper back (aOR = 5.09), and lower back pain (aOR = 3.67) at p < 0.05. Using these factors to formulate safety measures to reduce MSD risk, the minimization of sharp turns and abrupt changes in elevation in designing the haul roads, scheduled maintenance practices, and ergonomic seat design were found as important safety measures in this study. CONCLUSION: Our unique methodological approach in occupational health research could be highly beneficial for tailoring safety measures at the unit level with minimal effort.

Development of an intervention program to reduce whole-body vibration exposure based on occupational and individual determinants among dumper operators.

Objectives. Studies related to a systematic approach for intervention design to reduce whole-body vibration (WBV) exposure are scarce. This study presents a systematic approach to identifying, selecting and prioritizing safety interventions to fulfill that research gap. Methods. A total of 130 vibration readings for dumper operators were taken from two surface iron ore mines to identify significant determinants of WBV exposure. Initially, age, weight, seat design, awkward posture, machine's age, load tonnage, dumper speed and haul road condition were hypothesized as determinants. Data were collected through standardized questionnaires and field-based observation. A multivariate statistical approach was applied for the practical use of the intervention program. Results. As some of the hypothesized factors were correlated, exploratory factor analysis (EFA) followed by multiple linear regression (MLR) was used to investigate their association with WBV exposure. As per EFA results, hypothesized factors were clubbed under individual, ergonomics and occupational factors. Occupational and ergonomics factors were found to be significantly associated with WBV exposure through MLR and used to form safety interventions to reduce WBV exposure. Conclusions. Our methodological approach is original in the occupational health research area and can be helpful to tailor the safety interventions for the unit level with minimum effort.

Schizo-Net: A novel Schizophrenia Diagnosis framework using late fusion multimodal deep learning on Electroencephalogram-based Brain connectivity indices.

Schizophrenia (SCZ) is a serious mental condition that causes hallucinations, delusions, and disordered thinking. Traditionally, SCZ diagnosis involves the subject's interview by a skilled psychiatrist. The process needs time and is bound to human errors and bias. Recently, brain connectivity indices have been used in a few pattern recognition methods to discriminate neuro-psychiatric patients from healthy subjects. The study presents Schizo-Net, a novel, highly accurate, and reliable SCZ diagnosis model based on a late multimodal fusion of estimated brain connectivity indices from EEG activity. First, the raw EEG activity is pre-processed exhaustively to remove unwanted artifacts. Next, six brain connectivity indices are estimated from the windowed EEG activity, and six different deep learning architectures (with varying neurons and hidden layers) are trained. The present study is the first which considers a large number of brain connectivity indices, especially for SCZ. A detailed study was also performed that identifies SCZ-related changes occurring in brain connectivity, and the vital significance of BCI is drawn in this regard to identify the biomarkers of the disease. Schizo-Net surpasses current models and achieves 99.84% accuracy. An optimum deep learning architecture selection is also performed for improved classification. The study also establishes that Late fusion technique outperforms single architecture-based prediction in diagnosing SCZ.

How Visual Stimuli Evoked P300 is Transforming the Brain-Computer Interface Landscape: A PRISMA Compliant Systematic Review.

Non-invasive Visual Stimuli evoked-EEG-based P300 BCIs have gained immense attention in recent years due to their ability to help patients with disability using BCI-controlled assistive devices and applications. In addition to the medical field, P300 BCI has applications in entertainment, robotics, and education. The current article systematically reviews 147 articles that were published between 2006-2021*. Articles that pass the pre-defined criteria are included in the study. Further, classification based on their primary focus, including article orientation, participants' age groups, tasks given, databases, the EEG devices used in the studies, classification models, and application domain, is performed. The application-based classification considers a vast horizon, including medical assessment, assistance, diagnosis, applications, robotics, entertainment, etc. The analysis highlights an increasing potential for P300 detection using visual stimuli as a prominent and legitimate research area and demonstrates a significant growth in the research interest in the field of BCI spellers utilizing P300. This expansion was largely driven by the spread of wireless EEG devices, advances in computational intelligence methods, machine learning, neural networks and deep learning.

Tubulobulbar complex: cytoskeletal remodeling to release spermatozoa.

Tubulobulbar complexes (TBCs) are actin-based structures that help establish close contact between Sertoli-Sertoli cells or Sertoli-mature germ cells (spermatids) in the seminiferous tubules of the testes. They are actin-rich push-through devices that eliminate excess spermatid cytoplasm and prepare mature spermatids for release into the tubular lumen. Just prior to spermiation, the elongated spermatid interacts with the Sertoli cell via an extensive structure comprising various adhesion molecules called the apical ectoplasmic specialization which is partially replaced by the apical TBC, on the concave surface of the spermatid head. The sperm release process involves extensive restructuring, namely the disassembly and reassembly of junctions at the Sertoli-spermatid interface in the seminiferous epithelium. Based on the presence of different classes of molecules in the TBCs or the defects observed in the absence of TBCs, the main functions attributed to TBCs are elimination of excess spermatid cytoplasm, endocytosis and recycling of junctional molecules, shaping of the spermatid acrosome, and forming transient anchoring devices for mature spermatids before they are released. This review summarizes the recent findings that focus on the role of TBCs in cell cytoskeleton restructuring during sperm release in the testes and the molecular mechanism involved.

Limnochemistry and nutrient dynamics in Upper Lake, Bhopal, India.

In limnetic ecosystem, water quality depends upon physical, chemical, and biological factors. Effects of temperature, light scattering, and absorption by suspended and dissolved matter, transport, and mixing of nutrients within the lake are the significant factors as far as water quality is concerned. Nutrient loading into the lake and internal cycling of nutrients is always a matter of concern and critical to number of processes. During the winter season, heat and momentum transfer at the lake surface and the temperature-density relation of water destabilize the water column and drive vertical mixing and transport processes. The deepening of the surface layer produces nutrient transfer from the hypolimnion into the euphotic zone of epilimnion. It may also resuspend sediments that would have settled under stratified conditions, or redistribute particles that may still be in suspension. Thus, there exists a complex connection between the hydrodynamics and water quality issues. Present study is an effort to understand how seasonal changes in the limnetic ecosystem regulate the limnochemistry and movement of nutrient. The study revealed that significant variations of nutrients and organic load were observed between epilimnion and hypolimnion during summer season, and the lake was found in hyper-eutrophic condition throughout the study period.

Association between Whole-Body Vibration exposure and musculoskeletal disorders among dumper operators: A case-control study in Indian iron ore mines.

BACKGROUND: Dumper operators in mines worldwide are subjected to Musculoskeletal Disorders (MSDs) due to whole-body vibration exposure. This study evaluated the working-life-Whole-Body Vibration (WBV)-exposure and their association with various MSDs among dumper operators in mines which remains poorly addressed. METHODS: This case-control study in Indian iron ore mines was conducted to compare randomly selected 65 dumper operators and 65 office workers. Data were collected through face-to-face interviews using the Nordic Musculoskeletal Questionnaire (NMQ) and were analysed using logistic regression models. RESULTS: The study revealed that majority of the dumper operators were exposed to WBV exceeding the ISO-2631 limits. Compared with controls, the dumper operators had a much higher risk of upper back pain (age-overweight-adjusted odds ratio ORao = 5.37, 95% CI = 1.78-16.20), lower back pain (ORao = 2.72, 95% CI = 1.25-5.94), knee and leg pain (ORao = 3.68, 95% CI = 1.22-11.11), and having 2+ MSDs (ORao = 5.05, 95% CI = 1.88-13.51, vs. no MSDs). Working-life-WBV-exposure was higher among dumper operators having upper back pain (mean (SD) = 7.1 (1.91) vs. 5.7 (1.91), p < 0.01) and lower back pain (mean (SD) = 6.63 (2.10) vs. 5.55 (1.71), p < 0.01) compared to those without these MSDs. Older age was associated with higher risk of MSD pains. CONCLUSION: Dumper operators have excess MSDs due to high working-life-WBV-exposure. Their MSDs and working-life-WBV-exposure should be regularly evaluated and reduced.

Deep-Precognitive Diagnosis: Preventing Future Pandemics by Novel Disease Detection With Biologically-Inspired Conv-Fuzzy Network.

Deep learning-based Computer-Aided Diagnosis has gained immense attention in recent years due to its capability to enhance diagnostic performance and elucidate complex clinical tasks. However, conventional supervised deep learning models are incapable of recognizing novel diseases that do not exist in the training dataset. Automated early-stage detection of novel infectious diseases can be vital in controlling their rapid spread. Moreover, the development of a conventional CAD model is only possible after disease outbreaks and datasets become available for training (viz. COVID-19 outbreak). Since novel diseases are unknown and cannot be included in training data, it is challenging to recognize them through existing supervised deep learning models. Even after data becomes available, recognizing new classes with conventional models requires a complete extensive re-training. The present study is the first to report this problem and propose a novel solution to it. In this study, we propose a new class of CAD models, i.e., Deep-Precognitive Diagnosis, wherein artificial agents are enabled to identify unknown diseases that have the potential to cause a pandemic in the future. A de novo biologically-inspired Conv-Fuzzy network is developed. Experimental results show that the model trained to classify Chest X-Ray (CXR) scans into normal and bacterial pneumonia detected a novel disease during testing, unseen by it in the training sample and confirmed to be COVID-19 later. The model is also tested on SARS-CoV-1 and MERS-CoV samples as unseen diseases and achieved state-of-the-art accuracy. The proposed model eliminates the need for model re-training by creating a new class in real-time for the detected novel disease, thus classifying it on all subsequent occurrences. Second, the model addresses the challenge of limited labeled data availability, which renders most supervised learning techniques ineffective and establishes that modified fuzzy classifiers can achieve high accuracy on image classification tasks.

Altered phosphorylation and distribution status of vimentin in rat seminiferous epithelium following 17ß-estradiol treatment.

Vimentin, type III intermediate filament, has stage-specific localization in the Sertoli cell. In the rat, during stages I-V and XI-XIV of the seminiferous epithelium, vimentin is localized in the perinuclear area with filaments projecting into the apical region toward the developing germ cells. These filaments decrease in length at stages VI-VII with perinuclear staining in stages VIII-IX, when spermiation occurs. Our earlier studies following 17ß-estradiol treatment to adult male rats demonstrated an increase in germ cell apoptosis, spermiation failure and disruption of Sertoli cell microfilaments and microtubules. The present study was undertaken to determine the stage-specific distribution of vimentin and its involvement in spermiation failure and germ cell apoptosis. Immunofluorescence studies revealed that in contrast to the perinuclear localization with small extensions in control stages VII-IX, long extensions radiating apically to the spermatids in deep recess were observed in the treated group. Immunoprecipitation studies showed marked absence of phosphorylated vimentin in stages VII-VIII in the treated group. Further, localization of plectin, cytoskeletal linker protein, showed decrease in all the stages of spermatogenesis following estradiol treatment. Interestingly, for the first time the localization of plectin in the tubulobulbar complex was observed. In conclusion, the study suggests that estradiol treatment leads to an effect on vimentin phosphorylation, which could have inhibited the disassembly of vimentin leading to retention of apical projection in stages VII-VIII. These effects could be presumably due to a decrease in plectin, affecting the reorganization of vimentin and therefore the apical movement of spermatids, leading to spermiation failure.

Synthesis of Macrocyclic Lactones and Dilactones Using Olive Oil.

Macrocyclic lactones have redolent characteristics of muscones that originate from the rectal musk organs of the musk deer. These lactones are the primary raw material in the flavor and fragrance industry and are also found within the cyclic frameworks of various bioactive molecules. Due to great demand, many efforts have been made for their synthesis; however, strategies generating a large number of macrocyclic analogues from renewable resources have not been fully realized and are urgently required. Here, we outline a sustainable, straightforward, and eco-friendly approach to synthesize high-valued macrocyclic lactones utilizing olive oil under greener reaction conditions. The outlined method allows us to turn biomass into valuable 12- to 29-membered lactones and dilactones.

Heterogeneous vanadium-catalyzed oxidative cleavage of olefins for sustainable synthesis of carboxylic acids.

The development of green and sustainable processes to synthesize active pharmaceutical ingredients and key starting materials is a priority for the pharmaceutical industry. A green and sustainable protocol for the oxidative cleavage of olefins to produce pharmaceutically and biologically valuable carboxylic acids is achieved. The developed protocol involves 70% aq. TBHP as an oxidant over a heterogeneous vanadium catalyst system. Notably, the synthesis of industrially important azelaic acid from various renewable vegetable oils is accomplished. The catalyst could be recycled for up to 5 cycles without significant loss in yield and the protocol was successfully demonstrated at the gram-scale.

Seasonal and spatial variation of Yamuna River water quality in Delhi, India.

Yamuna river pollution has been extensively studied with regard to some selected parameters in five locations at Palla, Nizamuddin Midstream, Nizamuddin Quarter Stream, Agra Canal Midstream, and Agra Canal Quarter Stream in Delhi, India. Seasonal and location-wise variation of pollutants namely dissolve oxygen (DO), biochemical oxygen demand (BOD), chemical oxygen demand (COD), total Kjeldahl nitrogen (TKN), ammonia (AMM), total coliform and fecal coliform were studied for 6 years during the period of 2000-2005. The study results revealed the lowest level of pollution during monsoon. The statistical analysis revealed a positive correlation between DO, BOD, COD, TKN, and AMM.

Clinical experience with arthroscopic suture pull technique in isolated PCL avulsion injuries.

OBJECTIVE: to assess twenty two cases of isolated PCL avulsion fractures from tibial insertion, arthroscopically treated with suture pull technique, and to evaluate achieved clinical outcomes in terms of radiographic laxometry (objective) and Lysholm scale (subjective). MATERIAL AND METHOD: Study includes 22 cases operated between April 2014 and March 2017. Patients less than 18 years old, presentation after 3 weeks of injury, concomitant injury in the same limb, with open wounds or with comminuted avulsed fragment were excluded from the study. All cases were MRI proven. All arthroscopic suture fixation technique was used in all cases. Follow up was done at 3 weeks, 6 weeks, 3 months, 6 months and 12 months. Mean follow up was one year. Subjective complaints, Knee flexion, Lysholm score and stress radiographs were noted. RESULTS: Average Lysholm score was 96.3. Seventeen patients had excellent results and Five had good results based on Lysholm scores. In two patients, grade 2 laxity (5-10 mm) was present on stress radiographs but there were no clinical complaints. All patients achieved osseous union and had no functional limitation. Three Patients developed arthrofibrosis initially but gained functional range later. CONCLUSION: Arthroscopic suture fixation method for PCL avulsion fracture from tibia is a good and safe method of choice for fixation.

Synthesis of Bioactive Complex Small Molecule-Ciprofloxacin Conjugates and Evaluation of Their Antibacterial Activity.

Conjugates between pharmaceuticals and small molecules enable access to a vast chemical space required for the discovery of new lead molecules with modified therapeutic potential. However, the dearth of specific chemical reactions that are capable of functionalizing drugs and bioactive natural products presents a formidable challenge for preparing their conjugates. Here, we report a support-free CuI-nanoparticle-catalyzed strategy for conjugating electron-deficient and electron-rich terminal alkynes with a ciprofloxacin methyl ester. Our conjugation technique exploits the late-stage functionalization of bioactive natural products such as tocopherol, vasicinone, amino acids, and pharmaceuticals such as aspirin and paracetamol to provide conjugates in excellent yields under mild and green conditions. This protocol also enabled the synthesis of (hetero)arene-ciprofloxacin 1,4-disubstituted 1,2,3-triazoles in good yields and high regioselectivities. These synthesized ciprofloxacin conjugates were evaluated in vitro for their antibacterial activity against a panel of relevant bacteria. A significant number of conjugates showed comparable activity against Gram-positive and Gram-negative bacteria. Moreover, some conjugates exhibited less toxicity than ciprofloxacin against two mammalian cell lines, suggesting the utility for the future investigation of these compounds for in vivo efficacy and pharmacokinetic studies.

Formic Acid-Driven Rapid and Green Anti-Markovnikov Hydrothiolation of Styrenes.

A novel formic acid-assisted rapid and efficient route for C-S bond construction via the thiol-ene reaction has been reported. Exclusively, the anti-Markovnikov product was obtained in good to excellent yield using the developed protocol. Various styrenes and thiols bearing different functionalities were well tolerated. The reaction also provided a good yield of sulfones in a one-pot two-step protocol. The developed method is operationally simple, green, metal-free, solvent-free, and having a high atom economy with high regioselectivity.

2-Aminoquinazolin-4(3H)-one as an Organocatalyst for the Synthesis of Tertiary Amines.

The potential of 2-aminoquinazolin-4(3H)-one as an organocatalyst for the activation of aldehydes via noncovalent interaction for the synthesis of tertiary amines using formic acid as a reducing agent is reported for the first time. The developed protocol demonstrated a dilated substrate scope for aromatic and aliphatic amines with aromatic and aliphatic aldehydes. Furthermore, the current method was also fruitful for the derivatization of ciprofloxacin and its derivative in good to excellent yields.

Evaluation of functional outcome of pilon fractures managed with limited internal fixation and external fixation: A prospective clinical study.

INTRODUCTION: The management of pilon fractures is controversial primarily due to the high rate of complications irrespective of the mode of treatment. Limited internal fixation with external fixation is associated with minimal soft tissue handling. This may reduce the chances of wound dehiscence and infection. This study was designed to evaluate the functional and clinical outcomes in patients treated with limited internal fixation combined with external fixation in pilon fractures. MATERIAL AND METHODS: This study was conducted as a prospective clinical study on 56 skeletally mature patients with closed fractures with poor skin condition, and with open grade 1 and grade 2 distal tibial intra-articular fractures. All patients were treated with combined limited internal fixation and ankle spanning external fixation. RESULTS: All fractures in this series united with an average time period of union of 18.3weeks (ranging from 13 weeks to 30 weeks). There was no non-union in any case. There was malunion in 4 cases, varus malunion (>5 degree) in 2 cases and recurvatum in another 2 cases). Excellent to good functional results were observed in 88% cases based on the modified Ovadia and Beals score. The mean ankle dorsiflexion and planter flexion movements were 10.2±5.3 degrees and 27.4±7.2 degrees respectively. infections occurred in 6 patients which included 4 pin tract infections and 2 superficial wound infection, all 6 healed after removal of pin tract and with oral antibiotics. CONCLUSION: The technique of combined external fixation with internal fixation is safe and effective management option for intra-articular distal tibial fractures.