Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines

Curcumin, a well-known chemopreventive agent, has been shown to suppress the proliferation of a wide variety of tumor cells through a mechanism that is not fully understood. Cyclin E, a proto-oncogene that is overexpressed in many human cancers, mediates the G(1) to S transition, is a potential target of curcumin. We demonstrate in this report a dose- and time-dependent down-regulation of expression of cyclin E by curcumin that correlates with the decrease in the proliferation of human prostate and breast cancer cells. The suppression of cyclin E expression was not cell type dependent as down-regulation occurred in estrogen-positive and -negative breast cancer cells, androgen-dependent and -independent prostate cancer cells, leukemia and lymphoma cells, head and neck carcinoma cells, and lung cancer cells. Curcumin-induced down-regulation of cyclin E was reversed by proteasome inhibitors, lactacystin and N-acetyl-L-leucyl-L-leucyl-L-norleucinal, suggesting the role of ubiquitin-dependent proteasomal pathway. We found that curcumin enhanced the expression of tumor cyclin-dependent kinase (CDK) inhibitors p21 and p27 as well as tumor suppressor protein p53 but suppressed the expression of retinoblastoma protein. Curcumin also induced the accumulation of the cells in G1 phase of the cell cycle. Overall, our results suggest that proteasome-mediated down-regulation of cyclin E and up-regulation of CDK inhibitors may contribute to the antiproliferative effects of curcumin against various tumors.     

Carcinoid tumor and intravenous octreotide infusion during labor and delivery

There are limited numbers of reports concerning the management of pregnancy complicated by carcinoid tumors. Octreotide, the synthetic analogue of somatostatin, has been found to be beneficial in preventing the perioperative exacerbation of carcinoid syndrome. We present a case of the successful use of neuraxial analgesia/anesthesia for labor and vaginal delivery in a symptomatic parturient afflicted with carcinoid syndrome, who received an intravenous infusion of octreotide throughout labor and vaginal delivery.     

Detection of mycobacterium tuberculosis by nested polymerase chain reaction in a case of subconjunctival tuberculosis.

PURPOSE: To highlight the importance of nested polymerase chain reaction (PCR) in the detection of Mycobacterium tuberculosis in a case of subconjunctival tuberculosis. METHODS: We report a case of a 60-year-old man with subconjunctival nodule in the right eye for duration of 6 weeks. Biopsy of the nodule showed a granuloma with extensive caseation necrosis. Ziehl Neelsen staining for acid-fast bacilli (AFB) was negative. However, because of a strong suspicion of Mycobacterium infection, PCR for M. tuberculosis genome was done, using the nested PCR technique. RESULTS: Polymerase chain reaction for M. tuberculosis showed amplification of Mycobacterium tuberculosis genome with the nested PCR technique. CONCLUSION: Our case indicates that PCR can be a valuable tool in the diagnosis of conjunctival tuberculosis from paraffin sections.     

Immune Checkpoint Inhibition With Chemoradiotherapy in Stage III Non–small-cell Lung Cancer: A Systematic Review and Meta-analysis of Safety Results

The role of immune checkpoint inhibitors (ICIs) administered concurrently with or after definitive chemoradiation (CRT) in stage III non–small-cell lung cancer (NSCLC) has been detailed in several studies. We performed a systematic review to determine pneumonitis rates using ICIs with CRT. MEDLINE and EMBASE databases were searched using keywords and MeSH terms. Studies using anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) therapy, either sequentially or concurrently with CRT, for patients with stage III NSCLC were included. A meta-analysis of pneumonitis rates was performed based on weighted pooled proportion, using random-effects models. Weighting was performed by the inverse variance or standard error of event rates. Comparative analysis between groups was performed. Odds ratios (OR) were used as the primary summary statistics.A total of 13 studies were identified (6 prospective clinical trials and 7 real-world reports). Rates of grade ≥ 3 pneumonitis were significantly higher in clinical trials using anti–PD-1 therapy compared with PD-L1 inhibitors (8.6%; 95% confidence interval [CI], 6.2%-11.9% vs. 4.4%; 95% CI, 3.0%-6.6%; OR, 2.0; P = .01). Clinical trials using concurrent ICI therapy with CRT had greater rates of grade 2 pneumonitis compared with sequential administration (23.0%; 95% CI, 15.8%-32.3% vs. 11.0%; 95% CI, 6.6%-17.8%; OR, 0.42; P = .02). Higher rates of grade ≥ 3 pneumonitis were observed in real-world studies compared with clinical trials involving sequential PD-L1 therapy (9.9%; 95% CI, 5.3%-17.9% vs. 4.4%; 95% CI, 2.9%-6.7%; OR, 0.43; P < .01).The suggestion of increased pneumonitis with a concurrent ICI strategy and using anti–PD-1 therapies warrants further consideration in future comparative studies.     

Sandwich Thyroplasty: A Novel Technique for Simplifying Medialization of Vocal Fold Using Silicone Implant in Paralytic Dysphonia with Modification of Thyroplasty Window

A novel technique of thyroplasty—Sandwich thyroplasty—described, with modification of Isshiki’s thyroplasty window to overcome the problems of securing and stabilising the silicone implant in the window thus simplifying the medialization of the vocal fold. Seventy five patients diagnosed with paralytic dysphonia of varied etiology, attending Sri Sathya Sai Institute of ORL, Guntur, India from January 2005 to January 2012, were subjected to this new technique. Medialization of vocal fold was achieved by sandwiching and stabilising a silicone implant between a superiorly based cartilaginous hinged door and the inner perichondrium of the modified thyroplasty window. Results were analysed based upon pre and postoperative voice handicap index, maximum phonation time readings and video-stroboscopic findings. The results were statistically significant with no untoward complications. Sandwich thyroplasty technique facilitated easier fixation and stabilization of silicone implant avoiding difficult and time consuming, techniques involving flanges or sutures.     

Tailoring of the electronic property of Zn-BTC metal–organic framework via ligand functionalization: an ab initio investigation

Metal–organic frameworks (MOFs) are porous materials of recent interest due to their promising properties for technological applications. In this paper, the structure–property relationships of pristine and functionalized Zn-BTC (Zn₃(BTC)₂) MOFs are investigated. The results based on density functional theory (DFT) find that MOFs with coordinatively saturated secondary building units (SBU) are metallic, and MOFs with coordinatively unsaturated SBU are semi-conducting. The ligand functionalization with electron acceptor (cyano-) and electron donor (amino-) groups appears to tailor the electronic properties of Zn-BTC MOFs; amino-functionalization led to a significant upward shift of the band-edges whereas cyano-functionalization yields shifting of band-edges in the opposite direction, which led to a narrowing of the band gap. Modifying the electronic properties through such ligand functionalization design principles can be useful in engineering MOFs for gas sensing and device applications.

The structure–property relationships of pristine and functionalized Zn-BTC (Zn₃(BTC)₂) metal–organic frameworks are investigated.     

Evaluation of the prevalence and severity of pain in patients with stable chronic heart failure

AIM:To evaluate the prevalence and severity of pain in patients with chronic stable heart failure(HF) in an outpatient clinic setting.METHODS:This is a cross-sectional study evaluating symptoms of generalized or specific pain in patients with chronic stable heart failure.A standardized questionnaire(Edmonton Symptom Assessment System) was administered during a routine outpatient clinic visit.The severity of pain and other symptoms were assessed on a 10 point scale with 10 being the worst and 0 representing no symptoms.RESULTS:Sixty-two patients [age 56 ± 13 years,51 males,11 females,mean ejection fraction(EF) 33% ± 17%] completed the assessment.Thirty-two patients(52%) reported any pain of various character and location such as chest,back,abdomen or the extremities,with a mean pain score of 2.5 ± 3.1.Patients with an EF less than 40%(n = 45,73%) reported higher pain scores than patients with an EF greater than 40%(n = 17,27%),scores were 3.1 ± 3.3 vs 1.2 ± 1.9,P < 0.001.Most frequent symptoms were tiredness(in 75% of patients),decreased wellbeing(84%),shortness of breath(SOB,76%),and drowsiness(70%).The most severe symptom was tiredness with a score of 4.0 ± 2.8,followed by decreased wellbeing(3.7 ± 2.7),SOB(3.6 ± 2.8),and drowsiness(2.8 ± 2.8).CONCLUSION:Pain appears to be prevalent and significantly affects quality of life in HF patients.Adequate pain assessment and management should be an integral part of chronic heart failure management.     

Bone sarcoidosis

Sarcoidosis is a disease that exhibits extremely heterogeneous clinical manifestations. Although the lungs are the most commonly involved organs, the extension of the granulomatous process may also affect the bones. Almost any bone can be involved; curiously, the small bones of the hands and feet are most frequently affected. Diagnosis and recognition of osseous sarcoidosis is easy, but the therapy is disappointing. Corticosteroids and antimalarials may control pain and swelling, but usually do not influence the course of osseous sarcoidosis.