Synthesis of imidazole-pyrazole conjugates bearing aryl spacer and exploring their enzyme inhibition potentials.

Developing improved enzyme inhibitors is an effective therapy to counter various diseases. Aiming to build up biologically active templates, a new series of bis-diazoles conjugated with an aryl linker was designed and prepared through a convenient synthetic approach. Synthesized derivatives 6(a-m), having different substitutions at the 2nd position of the imidazole nucleus, depict the scope of present study. These compounds were characterized through spectroscopic methods and further examined for their in vitro enzyme inhibitory potentials against two selected enzymes: α-glucosidase and lipoxygenase (LOX). Overall, this series was found to be effective against α-glucosidase and moderately active against LOX enzyme. Compound 6k was the most potent α-glucosidase inhibitor with IC50 = 54.25 ± 0.67 µM as compared to reference drug acarbose (IC50 = 375.82 ± 1.76 µM). The docked conformation revealed the involvement of substituent's heteroatoms with amino acid residue Gly280 through hydrogen bonding. The most active LOX inhibitor was 6a with IC50 = 41.75 ± 0.04 µM as compared to standard baicalein (IC50 = 22.4 ± 1.3 µM). Docking model of 6a suggested the strong interaction of imidazole's nitrogen with iron atom of the active pocket of enzyme. Other features like lipophilicity, bulkiness of compounds, pi-pi interactions and/or pi-alkyl interactions also affected the inhibiting potentials of all prepared scaffolds.

Evaluation of α-glucosidase inhibiting potentials with docking calculations of synthesized arylidene-pyrazolones.

Herein, condensation of aryl(hetaryl)pyrazole-4-carbaldehydes 1(a-c) with substituted pyrazolones 2(a-d) lead to the corresponding arylidene-pyrazolones 3(a-l) which were tested against α-glucosidase enzyme. The synthesized compounds displayed moderate to good activity. Among these, a coumarin derivative 3k exhibited excellent results (IC50 2.10 ±â€¯0.004 µM) in comparison to clinical drug acarbose (IC50 37.38 ±â€¯0.12 µM). The ligand-protein interactions were identified through docking and stabilizing energy calculations.

Comparison of Soft Tissue Chin Thickness in Adult Patients With Various Mandibular Divergence Patterns.

Objective This study aimed to compare the soft tissue chin (STC) thickness at different levels in patients presenting for orthodontic treatment with different vertical facial types. Materials and methods This comparative cross-sectional study was conducted at Sharif Medical & Dental College, Lahore, Pakistan, on 195 subjects. Patients presenting for orthodontic treatment, both genders, aged from 18 to 32 years, and Pakistani nationals were included. Patients with any craniofacial deformity, syndrome, cleft lip and palate, previous orthodontic or orthognathic treatment, and multiple missing teeth and prostheses in edentulous areas were excluded. Vertical facial patterns and STC thickness were recorded from pre-treatment lateral cephalograms. One-way analysis of variance (ANOVA) was applied to compare STC among various vertical facial patterns. Post-hoc analysis was done using the Tukey test. Results There were 126 females (64.62%) and 69 males (35.38%). The mean age was 21.66 ± 3.44 years. All three soft tissue chin thickness distances significantly differed among vertical facial patterns (p<0.001). Multiple comparisons show that the distance between soft and hard tissue pogonion was insignificant between low and normal angle facial heights (p=0.5). Similarly, no significant difference was observed for the distance between soft and hard tissue menton in low and normal angle subjects (p=0.4). The rest of the multiple comparisons were statistically significant (p<0.05). Conclusion The STC thickness is significantly associated with vertical facial divergence. While planning orthognathic surgery or genioplasty of the mandible, due consideration should be given to vertical divergence of the face to avoid unwanted facial changes.

Tannins as antimicrobial agents: Understanding toxic effects on pathogens.

"Tannins" are compounds that belong to a group of secondary metabolites found in plants. They have a polyphenolic nature and exhibit active actions as first line defenses against invading pathogens. Several studies have demonstrated the multiple activities of tannins, highlighting their effectiveness as broad-spectrum antimicrobial agents. Tannins have reported as antibacterial, antifungal, and antiviral compounds by preventing enzymatic activities and inhibiting the synthesis of nucleic acids. Additionally, tannins primarily strengthen the plant cell wall, making it almost impenetrable to harmful pathogens. Most tannins are synthesized via the phenylpropanoid pathway to become secondary metabolites. Increased uptake of tannins has the potential to provide permanent immunity to subsequent infections by strengthening cell walls and producing antimicrobial compounds. Tannins also demonstrate a synergistic response with other defense-related molecules, such as phytoalexins and pathogenesis-related proteins, including antimicrobial peptides. Studying the mechanisms mediated by tannins on pathogen behaviors would be beneficial in stimulating plant defense against pathogens. This understanding could help explain the occurrence of diseases and outbreaks and enable potential mitigation in both natural and agricultural ecosystems.

Comparison of Functional Outcome Between Intra-Articular Injection of Corticosteroid Versus Platelet-Rich Plasma in Frozen Shoulder: A Randomized Controlled Trial.

Background In this study, we compared the functional outcome of intra-articular injection of corticosteroid versus platelet-rich plasma (PRP) in patients with frozen shoulder (FS). Methodology This randomized controlled trial was conducted in the Department of Orthopedics, Mayo Hospital, Lahore, from January 2018 to December 2018.A total of 202 patients with FS aged 40 to 70 years were included. Patients with medical comorbidities such as chronic liver disease (assessed on history and serum bilirubin >2.0 mg/dl), chronic renal failure (assessed on history and serum creatinine >1.5 mg/dL), and chronic steroid use were excluded. Employing an anterior approach, subjects in groups A and B received one intra-articular injection of 2 mL PRP and 2 mL (80 mg) methylprednisolone acetate, respectively. Age, gender, duration of disease, and pre-injection and post-injection range of motion (ROM) (flexion, extension, abduction, external rotation, and internal rotation) were assessed. The University of California at Los Angeles Shoulder Score (UCLA) and visual analog scale (VAS) scores were measured and compared before and after the injection. All patients were followed at regular intervals post-therapy and the final functional outcome was measured after 12 weeks of therapy. Results Data were analyzed using SPSS version 20 (IBM Corp., Armonk, NY, USA). A p-value of 0.05 was considered significant when comparing flexion, abduction, external rotation, and internal rotation in both groups using the independent t-test. The ROM in group A (intra-articular PRP) improved significantly (p < 0.05) after injection compared to group B (intra-articular corticosteroid). The ROM after PRP for abduction was 147.09 ± 7.78, forward flexion 154.52 ± 6.48, external rotation 71.59 ± 7.43, and internal rotation 59.20 ± 3.96. The ROM in the steroid injection group for abduction was 129.07 ± 4.72, forward flexion 127.14 ± 7.87, external rotation 56.27 ± 5.93, and internal rotation 48.86 ± 4.90. Conclusions Intra-articular injection of PRP resulted in a substantial improvement in the VAS score, UCLA, and ROM when compared to intra-articular corticosteroid injection in patients with FS.

Evaluation of La(XT), a novel lanthanide compound, in an OVX rat model of osteoporosis.

PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of a novel lanthanum compound, La(XT), in an ovariectomized (OVX) rat model of osteoporosis. METHODS: Twenty-four ovariectomized female Sprague Dawley rats were divided into 3 groups receiving a research diet with/without treatment compounds (alendronate: 3 mg/kg; La(XT) 100 mg/kg) for three months. At the time of sacrifice, the kidney, liver, brain, lung and spleen were collected for histological examination. The trabecular bone structure of the tibiae was evaluated using micro-CT and a three-point metaphyseal mechanical test was used to evaluate bone failure load and stiffness. RESULTS: No significant differences were noted in plasma levels of calcium, phosphorus, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) between the La(XT) treatment compared to the non-treated OVX group. Alendronate-treated animals (positive control) showed higher BV/TV, Tb.N and lower Tb.Th and Tb.Sp when compared to the non-treated OVX group. Mechanical analysis indicated that stiffness was higher in the alendronate (32.88%, p = 0.04) when compared to the non-treated OVX group. Failure load did not differ among the groups. CONCLUSIONS: No kidney or liver toxicities of La(XT) treatments were found during the three-month study. The absence of liver and kidney toxicity with drug treatment for 3 months, as well as the increased trabecular bone stiffness are encouraging for the pursuit of further studies with La(XT) for a longer duration of time.

Dorsal pads versus nodules in normal population and Dupuytren's disease patients.

PURPOSE: There is ambiguity about using the term "knuckle pads" in Dupuytren's disease (DD). Clear definitions of dorsal knuckle pads and nodules are lacking and the prevalence of these 2 entities has not been determined. We sought to define these terms and investigate the distribution and frequency of dorsal knuckle pads and dorsal nodules in the normal volunteers and in DD patients. METHODS: We assessed 50 consecutive study patients with DD and a convenience sample group of 50 control patients without DD for dorsal cutaneous pads (DCP) (ie, thickening, sclerosis, and loss of skin elasticity) and dorsal Dupuytren's nodules (DDN) (ie, solid tumor-like masses over the digital joints). Demographic information was collected for both groups, including the extent of the disease in DD patients. We examined both groups for the presence of dorsal lesions and their characteristics, and the DD patients for other local and ectopic Dupuytren's lesions and for the level of diathesis. RESULTS: None of the control patients had DDN, whereas 9 DD patients had DDN (p = .002). Nine control patients had DCP, whereas 11 DD patients had DCP (p = .803) Among the 9 control patients with DCP, pads were predominantly over the proximal interphalangeal joints and tended to occur in men with physically demanding occupations, and in the dominant hand. The index and long fingers were most frequently affected. Six patients had only DCP, 4 had only DDN, and 5 had both DDN and DCP. In the control and study groups, the DCP characteristics and patients' demographic data were comparable. Patients with DDN were white men with physically undemanding occupations and had lesions over the proximal interphalangeal joints, most frequently in the index finger, with an average size of 6 mm. Neither DCP nor DDN were encountered in the thumb. CONCLUSIONS: Future studies should clearly distinguish between DCP and DDN. Although DDN are pathognomonic of DD, DCP demonstrates similar prevalence in normal and DD populations.

Population dynamics of microbial species under high and low ammonia nitrogen in the alternate layer bioreactor landfill (ALBL) approach.

Anaerobic landfill process is still believed to be a complex ecosystem due to the lack of knowledge on the functional activities of microbial species. This research sought to introduce a novel landfill bioreactor, named here as the alternate layer bioreactor landfill (ALBL) of fresh MSW (FW) and stabilized waste (CT) to avoid inhibitory conditions for the microbial species in anaerobic landfill. The stabilized waste layer in the bottom of landfill cell significantly changed microbial ecology of fresh MSW which in turn reduced the concentrations of NH4-N (29-31%) and VFAs (33-38%) in the ALBL approach, compared to fresh MSW disposal in sanitary landfill. The reduction of NH4-N favored early onset of methanogenesis within 6 weeks and methane (CH4) content of landfill gas increased from 11% to 40-50% (v/v), owing to the coexistence of Methanosarcinales (36-50%) and Methanomicrobiales (26-28%) archaea. The acetoclastic methanogenesis was achieved by reducing NH4-N toxicity in the ALBL.

Closing wedge osteotomy of abnormal middle phalanx for clinodactyly.

PURPOSE: To report a series of clinodactyly patients to report clinical and radiographic outcomes after closing wedge osteotomy and K-wire fixation of abnormal middle phalanges. METHODS: Twenty-five fingers from 17 patients were included in the study. All patients had more than 25 degrees of angulation and were treated with closing wedge osteotomy. Subjective and objective data with radiographic assessment were compared preoperatively and postoperatively. RESULTS: Male gender was predominant in our series (14 of the total 17 patients). Family history was positive for clinodactyly in 4 patients. The appearance of all fingers improved after surgery. Angular deformity was corrected on average from 33 degrees preoperatively to 9 degrees postoperatively. Analysis of radiographs showed deformity correction from 29 degrees preoperatively to 5 degrees postoperatively. Preoperative and postoperative arc of motion measurements were available for 10 patients. Distal interphalangeal joint arc of motion decreased from 84 degrees prior to surgery to 81 degrees after surgery, whereas proximal interphalangeal joint arc of motion was unchanged. CONCLUSIONS: Closing wedge osteotomy of the abnormal middle phalanx for clinodactyly has provided our patients with adequate correction of the deformity, improved hand function, and has provided high satisfaction for parents. This treatment is recommended for moderate (15 degrees to 30 degrees ) and severe (>30 degrees ) deformities.

Investigation of transmigrated mandibular canines.

INTRODUCTION: Canine transmigration is a rare orthodontic condition and it is relevant to perform the proper diagnose at an early age. OBJECTIVE: The aim of the current study was to find out the frequency of transmigrated mandibular canines (TRC) in orthodontic patients obtained from South Asian population of Pakistan origin. METHODS: Panoramic radiographs of 2,550 untreated orthodontic patients (1,248 males; 1,302 females) were included, to investigate the presence, site, and type of TRC. Any permanent mandibular canine that was found to be crossing the midline in panoramic radiographs was considered as TRC. RESULTS: The frequency of TRC was found to be 0.98%. TRC were only found unilaterally. No significance regarding gender and side was found. Nineteen TRC displayed a type 1 transmigratory pattern, while type 2 and type 5 transmigratory patterns were encountered in three patients. CONCLUSION: Frequency of transmigrated mandibular canines in the studied sample was 0.98%.

The S.An.A.® concept: Semi-aerobic, Anaerobic, Aerated bioreactor landfill.

Hybrid Bioreactor Landfills are designed to enhance and speed up biological processes, aiming at reducing the duration of post operational phase until landfill completion. S.An.A.® (Semi-aerobic, Anaerobic, Aerated) concept consists in a Hybrid Bioreactor featuring a first semi-aerobic phase to enhance the methane production occurring in the following anaerobic step and a forced aeration for the abatement of the residual emissions. At the end of the last step, semi-aerobic conditions are restored and flushing applied for leaching residual non-biodegradable compounds. Results of the application of S.An.A.® concept to a lab scale bioreactor system showed that pre-aeration was effective in controlling the concentration of VFA, increasing pH and stimulating methane production during anaerobic phase; in particular with intermittent airflow the methane potential was 50% higher respect to control reactors. Forced aeration reduced organic compounds and nitrogen concentration in leachate of an order of magnitude, better performing in low airflow reactors. S.An.A.® Hybrid bioreactors proved to be an efficient system both for increasing methane production and reaching landfill completion in shorter time, suggesting that with proper landfill management, the duration of post-closure care might be reduced by 25-35%.

Investigation of transmigrated mandibular canines

ABSTRACT Introduction: Canine transmigration is a rare orthodontic condition and it is relevant to perform the proper diagnose at an early age. Objective: The aim of the current study was to find out the frequency of transmigrated mandibular canines (TRC) in orthodontic patients obtained from South Asian population of Pakistan origin. Methods: Panoramic radiographs of 2,550 untreated orthodontic patients (1,248 males; 1,302 females) were included, to investigate the presence, site, and type of TRC. Any permanent mandibular canine that was found to be crossing the midline in panoramic radiographs was considered as TRC. Results: The frequency of TRC was found to be 0.98%. TRC were only found unilaterally. No significance regarding gender and side was found. Nineteen TRC displayed a type 1 transmigratory pattern, while type 2 and type 5 transmigratory patterns were encountered in three patients. Conclusion: Frequency of transmigrated mandibular canines in the studied sample was 0.98%.

RESUMO Introdução: a transmigração de caninos é uma condição ortodôntica rara, e é importante realizar seu adequado diagnóstico ainda em idade precoce. Objetivo: o objetivo do presente estudo foi avaliar a frequência da transmigração de caninos inferiores (TCI) em pacientes ortodônticos de origem paquistanesa. Métodos: com o objetivo de analisar a presença, o local e o tipo de TCI, foram avaliadas 2.550 radiografias panorâmicas pré-tratamento (1.248 homens, 1.302 mulheres) de pacientes ortodônticos. Foram considerados como TCI os caninos inferiores permanentes que, na radiografia, estivessem cruzando a linha média. Resultados: a frequência de TCI foi de 0,98%. Os achados demonstraram a presença de apenas TCI unilaterais, sem diferenças significativas em relação ao sexo e ao lado da arcada. O tipo 1 de transmigração foi encontrado em 19 pacientes e os tipos 2 e 5, em três pacientes. Conclusão: na presente amostra de origem paquistanesa, a frequência da transmigração de caninos inferiores foi de 0,98%.