Pyrazolidinone-Aided Ru(II)-Catalyzed Regioselective C-H Annulation with Allenes.

Regioselective annulation of allenes via C-H activation represents an elegant synthetic approach toward the construction of valuable scaffolds. Considering the importance of allenes, herein we developed an unprecedented Ru(II)-catalyzed highly regioselective redox-neutral C-H activation/(4 + 1)-annulation of 1-arylpyrazolidinones employing allenyl acetates to access pyrazolo[1,2-a]indazol-1-one derivatives. Additionally, allenyl cyclic carbonates, which were never tested in C-H activation, were utilized to construct a similar class of heterocycles having a pendent alcohol functionality. Notably, double C-H functionalization was achieved by a simple modification of reaction conditions. The synthetic significance of this methodology is underscored by late-stage modification of natural products, broad substrate scope, gram-scale synthesis, and postfunctionalizations.

Onco-pharmacist led evaluation of knowledge, attitude & practice (KAP) of safe handling cytotoxic drugs among health care professional's (HCP's) in tertiary care hospital: A hospital based interventional Study.

BACKGROUND: Cytotoxic drugs (CDs) are hazardous in nature. But it is necessary for the treatment in cancer patients. The healthcare professionals (HCPs) act as a facilitator through which the manufactured CDs reach the patient. However, safe handling of CDs becomes a primary concern not only for the recipients but also for the HCPs. METHODS: On Ethics committee approval, a prospective- interventional study was conducted among HCPs who are involved in handling of CDs in Oncology department of tertiary care hospital. The participants were screened for their eligibility criteria & 73 HCPs were recruited. The initial data was collected from the HCPs through interview & questionnaires. Later the participants were trained by oncology-pharmacist (7-8 months) for safe handling of CDs. After the training the participants were tested again through interview & questionnaires. RESULTS: 73 participants, (75%) nurses & (25%) physicians were included in the study. Among these participants, only 32.87% underwent training on reconstitution whereas 67.12% of the participants didn't undergo any training. The increase in mean score of KAP after the training was observed to be 3.44 ± 4.32, 1.23 ± 1.51 and 1.3 ± 1.01 respectively. CONCLUSION: The study concludes that mandatory requirement of training for HCPs using SOP's by qualified oncology-pharmacist to minimize the hazardous effects of CDs. It also highlights the improvisation techniques for handling of CDs will enhance the safety profile of HCPs & the patients, which helps in refining the quality of pharmaceutical and health care services provided in the cancer care settings.

Substrate-Dependent Denitrogenative Rearrangements of Rhodium Azavinyl Carbenes Involving 1,2-Aryl Migration.

Herein, we disclose substrate-dependent rearrangements of 4-substituted N-sulfonyl-1,2,3-triazoles under Rh(II)-catalysis via denitrogenation. The reaction pathways included key 1,2-aryl migration via the formation of intermediatory phenonium ion, which is elusive so far with Rh-azavinyl carbenes. Intriguingly, the transformations were completely dependent on the substituent present leading to different scaffolds like enaminones, pyrrol-3-ones, and azadienes. Hammett studies provided essential insights into the carbocationic intermediate formation. The developed methodology featured simple reaction conditions, excellent functional group compatibility, and broad substrate scope.

Regioselective Dichotomy in Ru(II)-Catalyzed C-H Annulation of Aryl Pyrazolidinones with 1,3-Diynes.

Herein, we present a substrate-controlled regiodivergent strategy for the selective synthesis of C3 or C2-alkynylated indoles via ruthenium-catalyzed [3 + 2]-annulation of readily available pyrazolidinones and 1,3-diynes. Remarkably, C3-alkynylated indoles were obtained in good yields when 1,4-diarylbuta-1,3-diynes were employed as the coupling partners. On the other hand, dialkyl-1,3-diynes led to the selective formation of C2-alkynylated indoles. The key features of the strategy are the operationally simple conditions and external-oxidant-free, broad-scope, and substrate-switchable indole synthesis. Scale-up reactions and further transformations expanded the synthetic utility of the protocol.

Biomechanical Testing of a Novel Device for Sutureless Nerve Repair.

Suboptimal nerve end alignment achieved with conventional nerve repair techniques may contribute to poor clinical outcomes. In this study, we introduce Nerve Tape®, a novel nerve repair device that integrates flexible columns of Nitinol microhooks within a biologic backing to entubulate, align, and secure approximated nerve ends. This study compares the repair strength of Nerve Tape with that of conventional microsuture repairs. Thirty small (2 mm) and 30 large (7 mm) diameter human cadaveric nerves were transected and repaired utilizing Nerve Tape or appropriate microsuture technique. Biomechanical testing was performed using a horizontal tensile tester. The repaired nerves were loaded until failure at a distraction rate of 40 mm/min, and the maximum failure load was determined. In the small nerve groups, the load-to-failure for Nerve Tape repairs (2.33 ± 0.66 N) was significantly higher than for suture repairs (1.22 ± 0.52 N; p < 0.05). In the large nerve groups, no significant difference in load-to-failure was found between Nerve Tape (7.45 ± 2.66 N) and suture repairs (5.82 ± 1.59 N: p = 0.12). Suture repairs tended to fail by rupture, whereas Nerve Tape failures resulted from microhook pullout. Nerve Tape is a novel nerve coaptation device that provides mechanical repair strength equal or greater to clinically relevant microsuture repairs.

Platinized graphene fiber electrodes uncover direct spleen-vagus communication.

Neural interfacing nerve fascicles along the splenic neurovascular plexus (SNVP) is needed to better understand the spleen physiology, and for selective neuromodulation of this major organ. However, their small size and anatomical location have proven to be a significant challenge. Here, we use a reduced liquid crystalline graphene oxide (rGO) fiber coated with platinum (Pt) as a super-flexible suture-like electrode to interface multiple SNVP. The Pt-rGO fibers work as a handover knot electrodes over the small SNVP, allowing sensitive recording from four splenic nerve terminal branches (SN 1-4), to uncover differential activity and axon composition among them. Here, the asymmetric defasciculation of the SN branches is revealed by electron microscopy, and the functional compartmentalization in spleen innervation is evidenced in response to hypoxia and pharmacological modulation of mean arterial pressure. We demonstrate that electrical stimulation of cervical and sub-diaphragmatic vagus nerve (VN), evokes activity in a subset of SN terminal branches, providing evidence for a direct VN control over the spleen. This notion is supported by adenoviral tract-tracing of SN branches, revealing an unconventional direct brain-spleen projection. High-performance Pt-rGO fiber electrodes, may be used for the fine neural modulation of other small neurovascular plexus at the point of entry of major organs as a bioelectronic medical alternative.

A Cross-Sectional Study of Quality of life, Psychiatric Illness, Perceived Social Support, Suicidal Risk and Selfesteem among patients with burns.

INTRODUCTION: Burns is one of the foremost causes of worldwide morbidity. Changes in appearance and functional impairment causes stigmatisation, impacting socio-occupational engagement and causing discomfort. AIMS AND OBJECTIVES: The study examined prevalence of psychiatric morbidity in post-burn patients, their perceived social support and self-esteem. It further assessed quality of life amongst post-burn patients. MATERIALS AND METHODS: A cross-sectional study was performed in a tertiary care centre where 100 patients were interviewed using purposive sampling technique over six months. Patients were administered a semi-structured questionnaire along with Mini International Neuropsychiatric Interview (MINI), Rosenberg's Self-Esteem Scale (RSES), Multidimensional Scale of Perceived Social Support (MSPSS) and WHO Quality Of Life - BREF (WHOQOL- BREF) scales. Contingency tables and Spearman's correlation helped to examine associations and correlations. Fischer's exact test, Mann Whitney test and ANOVA test were also used for statistical analysis. RESULTS AND DISCUSSION: There is high prevalence of psychiatric morbidity among patients with burns. The most common disorder was major depressive episode. Low self-esteem was found in one-third of patients with burns. Patients having low self-esteem had eleven times higher prevalence of suicidality. Patients with burns had high perceived social support. Quality of life in patients with burns depends on self-esteem, perceived social support and presence of psychiatric illnesses. CONCLUSION: This study illustrates the need for thorough evaluation and screening in patients with burns for psychopathology and self-esteem issues by primary physicians. Behaviour therapy, supportive psychotherapy, counselling and adequate socio-occupational rehabilitation of the patient should be done. Spreading awareness and organising support groups for patients with burns at the primary health centre level can be effective.

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines.

A metal- and additive-free, highly efficient, step-economical deoxygenative C2-heteroarylation of quinolines and isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-triazoles. A variety of α-triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products.

Rh(II)-Catalyzed Denitrogenative Transannulation of N-Sulfonyl-1,2,3-triazolyl Cyclohexadienones for the Synthesis of Benzofurans and Cyclopropa[cd]indole-carbaldehydes.

A rhodium-catalyzed intramolecular denitrogenative transannulation of N-sulfonyl-1,2,3-triazole-tethered cyclohexadienones has been achieved for the synthesis of benzofurans and cyclopropa[cd]indole-carbaldehydes in an operationally simple procedure. Remarkably, the reaction pathway is fully dependent on the linker heteroatom (O or N) present between the cyclohexadienone unit and triazole moiety. In the case of O-linked triazoles, a cascade sequence consisting of intramolecular cyclopropanation and rearrangement takes place, leading to the formation of benzofurans, while, in the case of N-linked triazoles, cyclopropa[cd]indole-carbaldehydes were isolated exclusively.

Rh(II)-Catalyzed Highly Diastereoselective Cascade Transannulation of N-Sulfonyl-1,2,3-triazoles and Vinyl Benzoxazinanones.

An efficient, Rh(II)-catalyzed, denitrogenative reaction of 4-vinyl benzoxazinanones with N-sulfonyl-1,2,3-triazoles has been developed for the synthesis of structurally diverse tricyclic 2-imidazolones in moderate to good yields with excellent diastereoselectivities. The reaction consists of the sequential formation of four new bonds: two C-N and two C-O bonds in a cascade fashion. The reaction works under operationally simple conditions and also represents the first catalytic nondecarboxylative cyclization of vinyl benzoxazinanones with triazoles.

Glial-derived growth factor and pleiotrophin synergistically promote axonal regeneration in critical nerve injuries.

The repair of nerve gap injuries longer than 3 cm is limited by the need to sacrifice donor tissue and the morbidity associated with the autograft gold standard, while decellularized grafts and biodegradable conduits are effective only in short nerve defects. The advantage of isogenic nerve implants seems to be the release of various growth factors by the denervated Schwann cells. We evaluated the effect of vascular endothelial growth factor, neurotrophins, and pleiotrophin (PTN) supplementation of multi-luminal conduits, in the repair of 3 and 4 cm nerve gaps in the rabbit peroneal nerve. In vitro screening revealed a synergistic regenerative effect of PTN with glial-derived neurotrophic factor (GDNF) in promoting sensory axon density, and motor axonal growth from spinal cord explants. In vivo, pleiotrophins were able to support nerve regrowth across a 3 cm gap. In the 4 cm lesions, PTN-GDNF had a modest effect in the number of axons distal to the implant, while increasing the mean axon diameter (1 ±â€¯0.4; p ≤ 0.001) over PTN or GDNF alone (0.80 ±â€¯0.2, 0.84 ±â€¯0.5; respectively). Some regenerated axons reinnervated muscle targets as indicated by neuromuscular junction staining. However, many were wrapped in Remak bundles, suggesting a delay in axonal sorting, explaining the limited electrophysiological function of the reinnervated muscle, and the modest recovery in toe spreading in the PTN-GDNF repaired animals. These results support the use of synergistic neurotrophic/pleiotrophic growth factors in long gap repair and underscore the need for re-myelination strategies distal to the injury site. STATEMENT OF SIGNIFICANCE: Nerve injuries due to trauma or tumor resection often result in long gaps that are challenging to repair. The best clinical option demands the use of autologous grafts that are associated with serious side effects. Bioengineered nerves are considered a good alternative, particularly if supplemented with growth factors, but current options do not match the regenerative capacity of autografts. This study revealed the synergistic effect of neurotrophins and pleiotrophins designed to achieve a broad cellular regenerative effect, and that GDNF-PTN are able to mediated axonal growth and partial functional recovery in a 4 cm nerve gap injury, albeit delays in remyelination. This report underscores the need for defining an optimal growth factor support for biosynthetic nerve implants.

Autoimmune Encephalitis Following Bone Marrow Transplantation.

BACKGROUND: Neurological complications, especially encephalopathy and seizures, are commonly seen in bone marrow transplant patients. Infections, chemotoxicity, graft versus host disease, or secondary central nervous system malignancies are the most common underlying etiologies. There is increased awareness that autoimmune encephalitis may cause neurological dysfunction in immunocompetent children. The potential role of such a mechanism in children undergoing bone marrow transplantation is unknown. METHODS: We report a boy who developed autoimmune encephalitis with voltage-gated potassium channel-associated and thyroid autoantibodies subsequent to transplantation. RESULTS: A 7-year-old boy presented with a change in behavior, poor attention, cognitive deficits, and abnormal movements 15 months after undergoing transplantation for idiopathic aplastic anemia. He had clinical and subclinical seizures and brain magnetic resonance imaging hyperintensities bilaterally in the uncal regions. His evaluation revealed high titers of voltage-gated potassium channel, leucine-rich glioma-inactivated 1 protein, and thyroglobulin antibodies suggestive of autoimmune limbic encephalitis. He showed significant improvement in behavior and neuropsychological testing and has remained seizure-free on levetiracetam after immunotherapy with corticosteroids and intravenous immunoglobulin. CONCLUSION: Systemic autoimmune manifestations in bone marrow transplant patients have been well-documented, but autoimmune encephalitis after transplantation has yet to be described in children.

A case of invasive papillary breast carcinoma: Fierce façade with favorable prognosis.

Invasive papillary carcinoma of the breast is a rare, distinct variant comprising approximately less than 1-2% of all newly diagnosed cases of breast carcinoma and is usually found in postmenopausal women with a more favorable prognosis. We report an unusual case in a 45-year-old perimenopausal female who came with a complaint of lump in right breast for duration of 1 year. A simple mastectomy was undertaken for histopathological study and immunohistochemistry (IHC) which showed characteristic features of an invasive papillary breast carcinoma. We present this case in view of its rarity and to highlight this clinicopathological subtype for its good prognosis and to avoid overtreatment.

Beta-amino alcohol derived beta-hydroxy- and beta-(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides: an ester-amide ligand structural model for the palladium-catalyzed allylic alkylation reaction.

A commercially available collection of beta-amino alcohols have been converted to their corresponding beta-hydroxy- and beta-(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides 11a-f and 12a-f and have been employed in the Tsuji-Trost asymmetric alkylation reaction with 1,3-diphenylpropenyl acetate. With the exception of ligands 11b and 11f, the beta-hydroxybenzoyloxy(o-diphenylphosphino)benzamide ligands 11a-f primarily afforded the (R)-enantiomer of the product. In contrast, the bis(phosphine) ligands 12a-f consistently afforded the (S)-enantiomer. The best ligand (12c) was derived from cis-(1R,2S)-2-amino-1,2-diphenyl-1-ethanol, and when applied in the asymmetric allylic alkylation reaction, it yielded the product in an enantiomeric ratio of 97.8.22 favoring the (S)-enantiomer. A computational study was conducted on the conformation that this ligand might adopt in the palladium-catalyzed alkylation reaction as compared to that of the Trost ligand 1a.

Menstrual disturbance and galactorrhea in people taking conventional antipsychotic medications.

Endocrine disturbances are emerging as major side effects of antipsychotic medications. Of particular note is the profile of menstrual disturbance and galactorrhea as a consequence of hyperprolactinemia (A. Weick & P. M. Haddad, 2003), a sequela of antidopaminergic action at the hypothalamopituitary axis. Research into the clinical aspects of this sensitive issue is sparse. The authors completed a cross-sectional descriptive study of 50 patients on conventional antipsychotic medications. The prevalence of menstrual disturbance was 54%, and the prevalence of amenorrhea was 12%. Symptoms of galactorrhea were present in 32% of patients. A history of pregnancy and childbirth was noted to be significantly associated with the development of galactorrhea (p = .01). The authors hypothesized that pregnancy and lactation might sensitize the hypothalamopituitary axis for further development of hyperprolactinemia due to medications.