Bisindole-based small molecules as transmembrane anion transporters and potential anticancer agents.

Few synthetic ion transporters have been reported incorporating indole as the core moiety. We have developed a novel bisindole-based transporter capable of efficient transmembrane anion antiport. This system induced cytotoxicity in MCF-7 breast cancer cells via chloride ion homeostasis disruption and the associated ROS generation, mitochondrial membrane depolarization, and lysosomal deacidification.

Photocontrolled activation of doubly o-nitrobenzyl-protected small molecule benzimidazoles leads to cancer cell death.

Artificial biomimetic chloride anionophores have shown promising applications as anticancer scaffolds. Importantly, stimuli-responsive chloride transporters that can be selectively activated inside the cancer cells to avoid undesired toxicity to normal, healthy cells are very rare. Particularly, light-responsive systems promise better applicability for photodynamic therapy because of their spatiotemporal controllability, low toxicity, and high tunability. Here, in this work, we report o-nitrobenzyl-linked, benzimidazole-based singly and doubly protected photocaged protransporters 2a, 2b, 3a, and 3b, respectively, and benzimidazole-2-amine-based active transporters 1a-1d. Among the active compounds, trifluoromethyl-based anionophore 1a showed efficient ion transport activity (EC50 = 1.2 ± 0.2 µM). Detailed mechanistic studies revealed Cl-/NO3- antiport as the main ion transport process. Interestingly, double protection with photocages was found to be necessary to achieve the complete "OFF-state" that could be activated by external light. The procarriers were eventually activated inside the MCF-7 cancer cells to induce phototoxic cell death.

NAD(P)H:Quinone Acceptor Oxidoreductase 1 (NQO1) Activatable Salicylamide H+ /Cl- Transporters.

NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a detoxifying enzyme overexpressed in tumors, plays a key role in protecting cancer cells against oxidative stress and thus has been considered an attractive candidate for activating prodrug(s). Herein, we report the first use of NQO1 for the selective activation of 'protransporter' systems in cancer cells leading to the induction of apoptosis. Salicylamides, easily synthesizable small molecules, have been effectively used for efficient H+ /Cl- symport across lipid membranes. The ion transport activity of salicylamides was efficiently abated by caging the OH group with NQO1 activatable quinones via either ether or ester linkage. The release of active transporters, following the reduction of quinone caged 'protransporters' by NQO1, was verified. Both the transporters and protransporters exhibited significant toxicity towards the MCF-7 breast cancer line, mediated via the induction of oxidative stress, mitochondrial membrane depolarization, and lysosomal deacidification. Induction of cell death via intrinsic apoptotic pathway was verified by monitoring PARP1 cleavage.

Bimodal structural tuning of pyrrole-2-carboxamide-based transmembrane ion transport systems.

The pyrrole-2-carboxamide moiety is well known for its presence in various natural products and its use in anion receptor systems. Here we assess the transmembrane anion transport activity of a series of substituted pyrrole-2-carboxamides and show them to be highly tuneable, versatile systems for anion transport by simple variations of pyrrole ring and amide substituents.

Low-glycemic foods with wheat, barley and herbs (Terminalia chebula, Terminalia bellerica and Emblica officinalis) inhibit α-amylase, α-glucosidase and DPP-IV activity in high fat and low dose streptozotocin-induced diabetic rat.

Wheat, barley or wheat + barley and herbs (Terminalia chebula, Terminalia bellerica and Emblica officinalis) based low-glycemic-index (low-GI) foods were developed and studied α-amylase, α-glucosidase and DPP-IV inhibition property in vitro and in the streptozotocin-induced diabetic rats. The GI of products ranged from 47 to 53 than control white bread (GI = 95). Total phenolic (20.1 ± 1 mg gallic acid/g dry wt.) and flavonoids (15.2 ± 1 mg quercetin/g dry wt.) were higher in wheat + barley than barley (17.2 ± 1; 13.6 ± 2) and wheat (16.9 ± 1; 14.9 ± 2) products. The in vitro α-amylase (4-10%), α-glucosidase (5-17%) and DPP-IV (3-26%) inhibition (IC50) of methanol extracts were higher than the aqueous extracts. The fasting blood glucose (50.85, 33.22 and 24.52%) and oral glucose tolerance (AUC = 32.1, 36.04, and 27.73%) was lower in barley, wheat, and wheat + barley fed diabetic groups than diabetic control group (1571.5 ± 13.5 mg/dL/120 min). Feeding wheat, barley, and W + B foods for 60 days inhibited the intestinal α-amylase (1.2, 1.1 and 1.5-folds), α-glucosidase (1.3, 1.2 and 1.7-folds) and DPP-IV (1.6, 1.5 and 2.1-folds) activity compared to diabetic control. Low-GI foods lower the systemic glucose level, inhibit the glycolytic enzymes and DPP-IV activity and hence desirable for diabetes management. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-021-05231-0.

Restoration of elective spine surgery during the first wave of COVID-19 : a UK-wide British Association of Spine Surgeons (BASS) prospective, multicentre, observational study.

AIMS: With resumption of elective spine surgery services in the UK following the first wave of the COVID-19 pandemic, we conducted a multicentre British Association of Spine Surgeons (BASS) collaborative study to examine the complications and deaths due to COVID-19 at the recovery phase of the pandemic. The aim was to analyze the safety of elective spinal surgery during the pandemic. METHODS: A prospective observational study was conducted from eight spinal centres for the first month of operating following restoration of elective spine surgery in each individual unit. Primary outcome measure was the 30-day postoperative COVID-19 infection rate. Secondary outcomes analyzed were the 30-day mortality rate, surgical adverse events, medical complications, and length of inpatient stay. RESULTS: In all, 257 patients (128 males) with a median age of 54 years (2 to 88) formed the study cohort. The mean number of procedures performed from each unit was 32 (16 to 101), with 118 procedures (46%) done as category three prioritization level. The majority of patients (87%) were low-medium "risk stratification" category and the mean length of hospital stay was 5.2 days. None of the patients were diagnosed with COVID-19 infection, nor was there any mortality related to COVID-19 during the 30-day follow-up period, with 25 patients (10%) having been tested for symptoms. Overall, 32 patients (12%) developed a total of 34 complications, with the majority (19/34) being grade 1 to 2 Clavien-Dindo classification of surgical complications. No patient required postoperative care in an intensive care setting for any unexpected complication. CONCLUSION: This study shows that safe and effective planned spinal surgical services can be restored avoiding viral transmission, with diligent adherence to national guidelines and COVID-19-secure pathways tailored according to the resources of the individual spinal units. Cite this article: Bone Jt Open 2021;2(12):1096-1101.

Mechanical, Fracture, and Microstructural Assessment of Carbon-Fiber-Reinforced Geopolymer Composites Containing Na2O.

For a sustainable environment, geopolymer (GPO) paste can be used in the construction industry instead of Portland cement. Nowadays, sustainable construction and high-efficacy composites are demanding. Therefore, in the present investigation, the mechanical and microstructural efficacy of carbon-fiber-reinforced fly ash-based GPO with different percentages of nano-sodium dioxide (NS) were studied. The investigated percentages of NS were 0%, 1%, 2%, 3%, and 4%. For all the samples, the carbon fiber content was kept the same at 0.5% by weight. Different percentages of NS for all five fabricated GPO composite pastes were assessed with scanning electron microscopy (SEM). Various mechanical parameters of GPO-the compressive strength, toughness modulus, hardness, toughness indices, impact strength, fracture toughness, flexural strength, and elastic modulus-were evaluated. The results revealed that the use of 3% NS was the most effective for ameliorating the mechanical, microstructural, and fracture behavior of GPO. The use of 3% NS in carbon-fiber-reinforced GPO paste showed the maximum improvements of 22%, 46%, 30%, 40%, 14%, 38.4%, 50.2%, 31%, and 64% for the compressive strength, flexural strength, elastic modulus, toughness modulus, hardness, compressive stiffness, bending stiffness, fracture toughness, and impact strength, respectively. The SEM study showed that the inclusion of NS improved the microstructure and delivered a denser GPO paste by improving the interfacial zones and quickening the polymerization reaction.

Five Year Follow up of Retrospective Cohort Comparing Structural and Functional Outcome of Arthroscopic Single-row ersus Double-row Suture Bridge Repair of Large Posterosuperior Rotator Cuff Tear in Patients Less than or Equal to 70 Years.

BACKGROUND: High re-tear rates after repairing large-sized posterosuperior rotator cuff tears remain a significant concern which may affect the clinical outcome. The most optimal type of repair (single versus double-row suture bridge) suited for large size tear remains debatable. METHODS: In a retrospective cohort study with a minimum of five years follow up, the structural and functional outcome of 103 patients with large size cuff tear repaired with single row (SR) or double row suture bridge (DRSB) were evaluated. The structural outcome was assessed with ultrasonography whereas functional outcome was evaluated with Constant Murley (CM) and American shoulder elbow score (ASES). RESULTS: There were 55 patients in the SR group and 48 patients in the DRSB group with a mean follow-up of 74.2 months (range, 60-96 months). While comparing the structural integrity in two groups, we found significantly lower re-tear rates in the DRSB group as compared to the SR group (10.4% vs. 32.7%; P=0.006). Also, there were more focal defects in the SR group (25.4%) than the DRSB group (8.3%). Overall, there was no significant difference in CM and ASES scores when the SR group was compared to DRSB. However, subgroup analysis between those with intact and retorn tendon revealed significant difference (P=0.0001) in the clinical scores. CONCLUSION: At a minimum of five years follow-up, the DRSB repair of large posterosuperior cuff tear resulted in superior structural healing over SR repair. Nevertheless, overall there was no significant functional difference between both the techniques. However, the functional outcome of the healed tendon subgroup was superior to retear tendon subgroup.

Synthesis of novel seven-membered carbasugars and evaluation of their glycosidase inhibition potentials.

Here, we report the synthesis of five novel seven-membered carbasugar analogs. We adopted a chiral-pool strategy starting from the cheap and readily available d-mannitol to synthesize these ring-expanded carbasugars. Apart from several regioselective protecting group manipulations, these syntheses involved Wittig olefination and ring-closing metathesis as the key steps. We observed an unprecedented deoxygenation reaction of an allylic benzyl ether upon treatment with H2/Pd during the synthesis. Preliminary biological evaluation of the carbasugars revealed that these ring expanded carbasugars act as inhibitors of various glycosidases. This study highlights the importance of the synthesis of novel ring expanded carbasugars and their biological exploration.

Personal protective equipment during the COVID-19 crisis: a snapshot and recommendations from the frontline of a university teaching hospital.

AIMS: The adequate provision of personal protective equipment (PPE) for healthcare workers has come under considerable scrutiny during the COVID-19 pandemic. This study aimed to evaluate staff awareness of PPE guidance, perceptions of PPE measures, and concerns regarding PPE use while caring for COVID-19 patients. In addition, responses of doctors, nurses, and other healthcare professionals (OHCPs) were compared. METHODS: The inclusion criteria were all staff working in clinical areas of the hospital. Staff were invited to take part using a link to an online questionnaire advertised by email, posters displayed in clinical areas, and social media. Questions grouped into the three key themes - staff awareness, perceptions, and concerns - were answered using a five-point Likert scale. The Kruskal-Wallis test was used to compare results across all three groups of staff. RESULTS: Overall, 315 staff took part in our study. There was a high awareness of PPE guidance at 84.4%, but only 52.4% of staff reported adequate PPE provision. 67.9% were still keen to come to work, despite very high levels of anxiety relating to contracting COVID-19 despite wearing PPE. Doctors had significantly higher ratings for questions relating to PPE awareness compared to other staff groups, while nursing staff and OHCPs had significantly higher levels of anxiety compared to doctors in relation to PPE and contracting COVID-19 (p < 0.05 using a Kruskal-Wallis test). CONCLUSION: We believe four recommendations are key to improve PPE measures and decrease anxiety: 1) nominated ward/department PPE champions; 2) anonymized reporting for PPE concerns; 3) formal PPE education sessions; and 4) drop-in counselling sessions for staff. We hope the insight and recommendations from this study can improve the PPE situation and maintain the health and wellbeing of the clinical work force, in order to care for COVID-19 patients safely and effectively.

COVID-19 and orthopaedic surgery: evolving strategies and early experience.

AIMS: COVID-19 has changed the practice of orthopaedics across the globe. The medical workforce has dealt with this outbreak with varying strategies and adaptations, which are relevant to its field and to the region. As one of the 'hotspots' in the UK , the surgical branch of trauma and orthopaedics need strategies to adapt to the ever-changing landscape of COVID-19. METHODS: Adapting to the crisis locally involved five operational elements: 1) triaging and workflow of orthopaedic patients; 2) operation theatre feasibility and functioning; 3) conservation of human resources and management of workforce in the department; 4) speciality training and progression; and 5) developing an exit strategy to resume elective work. Two hospitals under our trust were redesignated based on the treatment of COVID-19 patients. Registrar/consultant led telehealth reviews were carried out for early postoperative patients. Workflows for the management of outpatient care and inpatient care were created. We looked into the development of a dedicated operating space to perform the emergency orthopaedic surgeries without symptoms of COVID-19. Between March 23 and April 23, 2020, we have surgically treated 133 patients across both our hospitals in our trust. This mainly included hip fractures and fractures/infection affecting the hand. CONCLUSION: The COVID-19 pandemic is not the first disease outbreak affecting the UK, nor will it be the last. The current crisis has necessitated rapid development of new hospital guidelines and early adaptive strategies in our services. Protocols and directives need to be formalized keeping in mind that COVID-19 will have a long and protracted course until a definitive cure is discovered.

Clinical and Structural Outcomes after Arthroscopic Repair of Medium- to Massive-Sized Delaminated and Nondelaminated Rotator Cuff Tears.

INTRODUCTION: Current evidence is controversial about the outcomes after the repair of the delaminated versus nondelaminated rotator cuff tears. The objective of this study was to evaluate the factors affecting delamination of the cuff and clinical and structural outcomes after en masse arthroscopic repair of delaminated versus nondelaminated cuff of varying sizes. MATERIALS AND METHODS: A total of 233 patients with full-thickness posterosuperior cuff tears were divided in two groups: Group 1: Delaminated tears (n = 131) and Group 2: Nondelaminated tears (n = 102) of medium, large, and massive sizes. Both groups were evaluated by clinical scores (Constant-Murley [CM], American shoulder and elbow score [ASES]) and ultrasonography (USG), at a minimum followup of 2 years. RESULTS: The mean followup was 45.47 months. There was a weak but statistically significant linear correlation (P = 0.02) between the increasing size of tear and delamination, whereas increasing age and duration of symptoms did not correlate with increasing tendency of delamination. Final followup USG analysis revealed that there was no significant difference (P = 0.55) between healing rates of Group 1 and Group 2. Further taking various tear sizes into account, USG revealed no significant difference between the healing rates of two groups. The mean overall final postoperative CM and ASES scores of two groups did not show any significant difference (CM; P = 0.36, ASES; P = 0.4). However, the clinical outcome was significantly better in the completely healed group as compared to partially healed or retear group. CONCLUSIONS: A weak linear correlation between delamination and increasing size of the tear was noted. Although overall structural and clinical outcome is no different between two groups, the clinical outcomes of completely healed tear are better than partially healed ones. LEVEL OF EVIDENCE: Level III, Retrospective comparative.

Synthesis of Highly Substituted Furans by a Cascade of Formal anti-Carbopalladation/Hydroxylation and Elimination.

Highly substituted furans are generated by a cascade of formal anti-carbopalladation, attack of a nucleophilic hydroxy group, and aromatization by elimination of the emerging dihydrofuran derivative. Mono-, di-, and trisubstituted furans were obtained in good to excellent yields. When we attempted to access tetrasubstituted furan derivatives, an additional rearrangement was observed that resulted in the formation of chromenes. Follow-up chemistry shows the utility of TMS as a protecting group for the alkyne moiety.

A facile and green strategy for the synthesis of Au, Ag and Au-Ag alloy nanoparticles using aerial parts of R. hypocrateriformis extract and their biological evaluation.

A facile and green strategy is reported here to synthesize gold (Au), silver (Ag) and gold-silver (Au-Ag) alloy nanoparticles (NPs) through bio-reduction reactions of aqueous corresponding metal precursors mediated by extracts of aerial parts of R. hypocrateriformis, which act as both reducing and stabilizing agents, under microwave irradiation. UV-vis spectrophotometer, XRD, FT-IR, FESEM/TEM, TGA and EDAX analysis were used to characterize the obtained NPs. The formation of NPs is evident from their surface plasmon resonance peak observed at λmax=∼550, 450 and 500nm for Au, Ag and Au-Ag alloy NPs respectively. XRD pattern revealed that fcc structure, while FT-IR spectra signify the presence of phytochemicals adsorbed on NPs. Such a biofunctionalized NPs were characterized by their weight loss, 30% due to thermal degradation of plant phytochemicals observed in TG analysis. The spherical shape of Au, Ag and Au-Ag alloy NPs (∼10-50nm) is observed by FE-SEM/TEM images. EDAX analysis confirms the expected elemental composition. Moreover, these NPs showed enhanced antimicrobial, antioxidant, and anticancer activities, though it is more pronounced for Au-Ag alloy NPs, which is due to the combining effect of phytochemicals, Au and Ag metals. Thus, the biosynthesized NPs could be applied as effective growth inhibitors for various biomedical applications.

Aggressive nodular fascitis of the mandible in a child: a rare case report.

Nodular fascitis is a benign, reactive, fiboproliferative lesion that is thought to represent an over exuberant reaction to injury or inflammation. Its histological picture is very similar to fibro sarcoma. An accurate diagnosis is imperative to avoid unnecessary aggressive treatment. It occurs most commonly in upper extremities, and rarely in the maxillofacial region. We present a case of aggressive intraosseous nodular fascitis of the mandible involving the vital structures in the neck in a 10 year old boy.

An unusual case of Waldenstrom's macroglobulinemia presented with nasopharyngeal involvement.

We report a rare case of a 68-year-old male who presented with fever, weight loss, nasal blockage, and epistaxis. Examination revealed cervical and axillary lymphadenopathy with no evidence of organomegaly. On evaluation, bone marrow aspiration showed lymphoplasmacytic infiltration. The computed tomography of the neck showed nasopharyngeal mass and the biopsy of this mass and cervical lymph node showed lymphoplasmacytic lymphoma (LPL) with high serum IgM level. Hence, a diagnosis of Waldenstrom's macroglobulinemia (WM) was made. The patient received six cycles of chemotherapy with a combination of cyclophosphamide, vincristine, and prednisolone (COP regimen). Currently, the patient is under follow-up and in complete remission (CR), one year after completion of therapy. Nasopharyngeal involvement is extremely rare in WM, and hence we report this case.

Inflammatory pseudotumor of maxillary sinus: Mimicking as an aggressive malignancy.

Inflammatory pseudotumor is a rare entity in the head and neck region. Clinically it behaves as an aggressive lesion with extensive destruction but considered to be a benign reactive process. Because of its extensive involvement and infiltrative nature, it is confused as a malignancy. Most of them respond very well to corticosteroid and surgical excision.