Copper in Peru: Present status and future challenge

The copper mineralization in Peru is intimately associated with porphyry Cu deposits and subdivides into three porphyry Cu belt as Paleocene, Eocene-Oligocene, and Miocene. Up to now, the total copper production from them reach 28 Mt Cu. The total copper production from the Paleocene Cu belt, including Toquepala, Cuajone, and Cerro Verde, accounts for approximately 57% of total copper production from Peru. But focusing mineral exploration on middle southern (Eocene-Oligocene) and northwestern part (Miocene) of Peru results in new discoveries, including La Granja, El Galeno, Las Bambas, Toromocho, and Rio Blanco, which have an estimated annual production more than 200,000 t Cu. In addition to them, thirteen Cu deposits are discovered from the Paleocene, Eocene-Oligocene, and Miocene Cu belts. Thus, Peru is supposed to produce Cu production from 2014 and increases annual production from 143 Mt Cu in 2012 to 490 Mt Cu in 2019. Due to new discoveries, it is expected that mineral exploration activities in Peru are likely to move from Paleocene Cu belt to Eocene-Oligocene and Miocene Cu belts

Chuna (or Tuina) Manual Therapy for Musculoskeletal Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective. To review the literature and systematically evaluate the effectiveness of Chuna (or Tuina) manual therapy (C[T]MT) on pain and function for musculoskeletal disorders. Methods. We searched 15 English, Chinese, Japanese, and Korean databases using relevant keywords. All randomized controlled trials (RCTs) of C(T)MT for musculoskeletal disorders were considered, and we limited analyses to studies with a low-risk bias for randomization and/or allocation concealment. Results. Sixty-six RCTs with 6,170 participants were included. One sham-controlled RCT showed that C(T)MT relieved pain more effectively than a sham control (SMD -3.09 [-3.59, -2.59]). For active-controlled RCTs, pooled meta-analysis showed that C(T)MT had statistically significant effects on pain reduction, especially compared to traction (P<0.00001), drugs (P=0.04), and physical therapies (P<0.0001). For functional improvement, combined effects of C(T)MT with drugs (P=0.04) and traction (P=0.05) also showed similar positive effects. Conclusions. This systematic review suggests that C(T)MT is safe and effective for pain reduction and functional improvement for musculoskeletal diseases; however, the evidence for functional improvement was not as strong as for pain reduction. For future studies, high-quality RCTs such as sham-controlled studies with standardized interventions are needed to provide sufficient evidence on the effects of C(T)MT for musculoskeletal diseases. Protocol registration number is CRD42016038307 04/07/2016

cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells

Background: The ataxia–telangiectasia mutated (ATM) protein kinase plays a central role in coordinating the cellular response to radiation-induced DNA damage. cAMP signaling regulates various cellular responses including metabolism and gene expression. This study aimed to investigate the mechanism through which cAMP signaling regulates ATM activation and cellular responses to ionizing radiation in lung cancer cells. Methods: Lung cancer cells were transfected with constitutively active stimulatory G protein (GαsQL), and irradiated with γ-rays. The phosphorylation of ATM and protein phosphatase 2A was analyzed by western blotting, and apoptosis was assessed by western blotting, flow cytometry, and TUNNEL staining. The promoter activity of NF-κB was determined by dual luciferase reporter assay. BALB/c mice were treated with forskolin to assess the effect in the lung tissue. Results: Transient expression of GαsQL significantly inhibited radiation-induced ATM phosphorylation in H1299 human lung cancer cells. Treatment with okadaic acid or knock down of PP2A B56δ subunit abolished the inhibitory effect of Gαs on radiation-induced ATM phosphorylation. Expression of GαsQL increased phosphorylation of the B56δ and PP2A activity, and inhibition of PKA blocked Gαs-induced PP2A activation. GαsQL enhanced radiation-induced cleavage of caspase-3 and PARP and increased the number of early apoptotic cells. The radiation-induced apoptosis was increased by inhibition of NF-κB using PDTC or inhibition of ATM using KU55933 or siRNA against ATM. Pretreatment of BALB/c mice with forskolin stimulated phosphorylation of PP2A B56δ, inhibited the activation of ATM and NF-κB, and augmented radiation-induced apoptosis in the lung tissue. GαsQL expression decreased the nuclear levels of the p50 and p65 subunits and NF-κB-dependent activity after γ-ray irradiation in H1299 cells. Pretreatment with prostaglandin E2 or isoproterenol increased B56δ phosphorylation, decreased radiation-induced ATM phosphorylation and increased apoptosis. Conclusions: cAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-κB in lung cancer cells.This study was supported by a National Research Foundation (NRF) grant funded by the Korea government (MEST) (No. 2007–2001258), by Basic Science Research Program through the NRF funded by the Ministry of Education, Science and Technology (2012R1A1A2044374), and a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (0720540).Peer Reviewe

Comparative effectiveness and safety of concomitant treatment with Chuna Manual Therapy and usual care for whiplash injuries: a multicenter randomized controlled trial

Objectives: We aimed to compare the effectiveness and safety of Chuna manual therapy combined with usual care to those of usual care alone for treating whiplash injuries. Design: A two-arm, parallel, assessor-blinded, multicenter pragmatic randomized clinical trial. Setting: Three hospitals in Korea. Participants: Overall, 132 participants between 19 and 70 years of age, involved in traffic accidents and treated at three hospitals in Korea, >2 but <13 weeks prior to enrollment, with neck pain consistent with whiplash-associated disorder grades I and II and a numeric rating scale score ≥5 were included. Interventions: Participants were equally and randomly allocated to the Chuna manual therapy and usual care (n = 66) or usual care (n = 66) groups and underwent corresponding treatment for three weeks. Primary and secondary outcome measures: The primary outcome was the number of days to achieve a 50% pain reduction. Secondary outcomes included areas under the 50% numeric rating scale reduction curve: pain, disability, quality of life, and safety. Results: The Chuna manual therapy + usual care group (23.31 ± 21.36 days; p = 0.01) required significantly fewer days to achieve 50% pain reduction compared to the usual care group (50.41 ± 48.32 days; p = 0.01). Regarding pain severity, functional index, and quality of life index, Chuna manual therapy and usual care were more effective than usual care alone. Safety was acceptable in both groups. Conclusions: In patients with subacute whiplash injury, Chuna manual therapy showed a rapid rate of recovery, high effectiveness, and safety

TRAIL Enhances Apoptosis of Human Hepatocellular Carcinoma Cells Sensitized by Hepatitis C Virus Infection: Therapeutic Implications

Hepatitis C virus (HCV) infection causes chronic liver diseases leading to hepatocellular carcinoma (HCC) and liver failure. We have previously shown that HCV sensitizes hepatocytes to mitochondrial apoptosis via the TRAIL death receptors DR4 and DR5. Although TRAIL and its receptors are selective targets for cancer therapy, their potential against HCC with chronic HCV infection has not been explored yet. Here we show that HCV induces DR4/DR5-dependent activation of caspase-8 leading to elevation of apoptotic signaling in infected cells and also present TRAIL effect in HCV-induced apoptotic signaling. HCV induced proteolytic cleavage of caspase-9 by stimulating DR4 and DR5, resulting in subsequent cleavage of caspase-3. Further, HCV-induced proteolytic cleavage in caspase-8, caspase-9, and caspase-3 was enhanced in the presence of recombinant TRAIL. HCV-induced cleavage in caspase-9 and increase in caspase-3/7 activity was completely suppressed by silencing of either DR4 or DR5. Perturbing DR4/DR5-caspase-8 signaling complex by silencing DR4 and DR5 or by chemical inhibitor specific to caspase-8 led to decrease of HCV-induced cleavage of poly(ADP-ribose) polymerase (PARP), a substrate for caspase-3 during apoptosis, indicating the functional role of caspase-8 in HCV-induced apoptotic signaling network. Furthermore, TRAIL enhanced PARP cleavage in apoptotic response induced by HCV infection, indicating the effect of TRAIL for the induction of selective apoptosis of HCC cells infected with HCV. Given the importance of apoptosis in HCC development, our data suggest that HCV-induced DR4 and DR5 may be considered as an attractive target for TRAIL therapy against HCC with chronic HCV infection

Point-of-care lactate: a predictor of emergency medicine resource use and outcomes in infants with diarrhea

Purpose Fluid therapy for diarrhea-induced dehydration inadvertently increases emergency department length of stay (EDLOS). To prevent this delay, we investigated the usefulness of triage using point-of-care (POC) lactate in infants with diarrhea. Methods This study was performed on infants with diarrhea who visited the emergency department from January 2019 through December 2020. According to the POC lactate concentration and the Korean Triage and Acuity Scale (KTAS) level, the infants were separately divided into the low (< 2 mmol/L), moderate (2-3.9), and high (≥ 4) lactate groups and the mild (KTAS 4-5) and severe (1-3) groups, respectively. Using these 2 group designations, we compared variables regarding the emergency medicine resource use and outcomes. To predict the prolonged EDLOS (≥ median value) we performed logistic regression and receiver operating characteristic analyses. Results A total of 540 infants were included. The median of EDLOS was 169 minutes (interquartile range, 103-220). Fluid therapy was more frequently performed in the high lactate group than in the low-moderate lactate groups (85.0% vs. 60.4%-73.6%; P = 0.025). The high lactate and severe groups respectively showed higher rates of hospitalization (40.0% vs. 3.8%-7.6% [P < 0.001] and 10.9% vs. 1.4% [P = 0.015]), and longer median EDLOS (259 minutes vs. 147-178 [P < 0.001] and 185 vs. 131 [P = 0.001]) compared to the low-moderate lactate and mild groups. Compared to the KTAS, lactate is more strongly associated with the prolonged EDLOS (lactate, adjusted odds ratio, 4.80 [95% confidence interval, 1.87-15.34] vs. KTAS, 3.52 [1.90-6.54]). The areas under curve for lactate and for the KTAS were 0.66 (0.60-0.73) and 0.62 (0.55-0.69), respectively (P = 0.058). Conclusion In infants with diarrhea, POC lactate can be a predictor of emergency medicine resource use and outcomes

Serous Retinal Detachment Following Combined Photodynamic Therapy and Intravitreal Bevacizumab Injection

We report a case of serous retinal detachment following combined photodynamic therapy (PDT) and intravitreal bevacizumab injection in subfoveal choroidal neovascularization (CNV)