Evaluation of spatial and temporal changes in illicit drug use in the Taipei metropolitan area via wastewater-based epidemiology.

Taiwan, identified as pivotal in the Asian drug trafficking chain, has been experiencing a surge in illicit drug-related issues. Wastewater-based epidemiology (WBE) has emerged as a promising approach for comprehensive evaluation of actual illicit drug usage. This study presents the first WBE investigation of illicit drug consumption in Taiwan based on the analysis of wastewater from four wastewater treatment plants (WWTPs) in the Taipei metropolitan area. Additionally, it demonstrates a high correlation between the amounts of illicit drugs seized and influent concentrations over an extended period of time. The reliability of solid-phase extraction and analysis via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was validated for 16 illicit drugs (methamphetamine, ketamine, cocaine, codeine, methadone, morphine, meperidine, fentanyl, sufentanil, para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), 3,4-methylenedioxymethamphetamine (MDMA), cathinone, methcathinone, mephedrone (MEPH), and 4-methylethcathinone (4-MEC)). Methamphetamine, ketamine, and 4-MEC were consistently detected in all wastewater samples, underscoring their prevalence in the Taipei metropolitan area. Biochemical oxygen demand (BOD) and ammonia nitrogen (ammonia N) were employed to reduce uncertainty in estimations of population size during back-calculation of illicit drug consumption. The results indicate that methamphetamine was the most consumed drug (175-740 mg day-1 1000 people-1), followed by ketamine (22-280 mg day-1 1000 people-1). In addition, urban-related WWTPs exhibited higher consumption of methamphetamine and ketamine than did the suburban-related WWTP, indicating distinct illicit drug usage patterns between suburban and urban regions. Moreover, an examination of temporal trends in wastewater from the Dihua WWTP revealed a persistent predominance of ketamine and methamphetamine, consistent with statistical data pertaining to seizure quantities and urine test results. The study provides encouraging insight into spatial and temporal variations in illicit drug usage in the Taipei metropolitan area, emphasizing the complementary role of WBE in understanding trends in illicit drug abuse.

Sunlight enhanced the formation of tribromomethane from benzotriazole degradation during the sunlight/free chlorine treatment in the presence of bromide.

The coexistence of free chlorine and bromide under sunlight irradiation (sunlight/FC with Br-) is unavoidable in outdoor seawater swimming pools, and the formation of brominated disinfection byproducts could act more harmful than chlorinated disinfection byproducts. In this study, benzotriazole was selected as a model compound to investigate the degradation rate and the subsequent formation of disinfection byproducts via sunlight/FC with Br- process. The rate constants for the degradation of benzotriazole under pseudo first order conditions in sunlight/FC with Br- and sunlight/FC are 2.3 ± 0.07 × 10-1 min-1 and 6.0 ± 0.7 × 10-2 min-1, respectively. The enhanced degradation of benzotriazole can be ascribed to the generation of HO•, bromine species, and reactive halogen species (RHS) during sunlight/FC with Br-. Despite the fact that sunlight/FC with Br- process enhanced benzotriazole degradation, the reaction results in increasing tribromomethane (TBM) formation. A high concentration (37.8 µg/L) of TBM was detected in the sunlight/FC with Br-, which was due to the reaction of RHS. The degradation of benzotriazole was notably influenced by the pH value (pH 4 - 11), the concentration of bromide (0 - 2 mM), and free chlorine (1 - 6 mg/L). Furthermore, the concentration of TBM increased when the free chlorine concentrations increased, implying the formation potential of harmful TBM in chlorinated seawater swimming pools.

Solar-driven persulfate degradation of caffeine and cephradine in synthetic human urine.

Urine source separation, as an innovative concept for the reuse of microlevel nutrients in human urine, has drawn increasing attention recently. Consequently, removing coexisting pharmaceuticals in urine is necessary for further reuse. This study is the first to apply the solar-driven persulfate process (Solar/PS) to the investigation of cephradine (CFD) and caffeine (CAF) degradation in synthetic human urine. The results showed that significantly more degradation of CFD and CAF occurs with the Solar/PS process than with persulfate oxidation and direct sunlight photolysis, respectively. The generated reactive species ·OH, SO4·-, O2·- and 1O2 were identified in the Solar/PS process. While SO4·- played a dominant role at pH 6, it played a minor role at pH 9 due to the lower amount generated under alkaline conditions. The presence of chloride and ammonia negatively impacted the photodegradation of both compounds. In contrast, bicarbonate exhibited no effect on CAF but enhanced CFD degradation owing to its amino-acid-like structure, which has a higher reactivity toward CO3·-. Although total organic carbon (TOC) was partially mineralized after 6 h of operation, no Microtox® toxicity was observed.

A protein kinase C α and ß inhibitor blunts hyperphagia to halt renal function decline and reduces adiposity in a rat model of obesity-driven type 2 diabetes.

Type 2 diabetes (T2D) and its complications can have debilitating, sometimes fatal consequences for afflicted individuals. The disease can be difficult to control, and therapeutic strategies to prevent T2D-induced tissue and organ damage are needed. Here we describe the results of administering a potent and selective inhibitor of Protein Kinase C (PKC) family members PKCα and PKCß, Cmpd 1, in the ZSF1 obese rat model of hyperphagia-induced, obesity-driven T2D. Although our initial intent was to evaluate the effect of PKCα/ß inhibition on renal damage in this model setting, Cmpd 1 unexpectedly caused a marked reduction in the hyperphagic response of ZSF1 obese animals. This halted renal function decline but did so indirectly and indistinguishably from a pair feeding comparator group. However, above and beyond this food intake effect, Cmpd 1 lowered overall animal body weights, reduced liver vacuolation, and reduced inguinal adipose tissue (iWAT) mass, inflammation, and adipocyte size. Taken together, Cmpd 1 had strong effects on multiple disease parameters in this obesity-driven rodent model of T2D. Further evaluation for potential translation of PKCα/ß inhibition to T2D and obesity in humans is warranted.

Reactive chlorine species in the enhanced degradation of UV stabilizers during the sunlight/free chlorine process.

Benzotriazole (BT) and 5-methyl-1H-benzotriazole (5-MeBT) are the most commonly used UV stabilizers and recalcitrant contaminants that are widely distributed in aquatic environments. The novelty of this study was to investigate the role of RCSs in the enhanced degradation of BT and 5-MeBT during the sunlight/free chlorine process. The results showed that sunlight/free chlorine could enhance the degradation of BT and 5-MeBT compared with that obtained with sunlight irradiation and chlorination alone, and this process was well described by pseudo-first-order kinetics. The degradation rate constants of BT and 5-MeBT during sunlight/free chlorine treatment at pH 7 were 0.094 ± 0.001 min-1 and 0.134 ± 0.002 min-1, respectively. The degradation rates further increased with increases in the chlorine dosage and under alkaline conditions (3.818 ± 0.243 min-1 for BT and 7.754 ± 0.716 min-1 for 5-MeBT at pH 9). The enhanced removal obtained during the sunlight/free chlorine process could be attributed to the generation of HO• and reactive chlorine species (RCSs), such as Cl• and ClO•. Under alkaline conditions, RCSs were the dominant reactive species, and their contribution increased from 21.2% to 98.7% with increases in the pH from 7 to 9; this phenomenon was due to changes in free chlorine and BT speciation. Radical scavenging tests further verified that BT was mainly decomposed by ClO•, and ClO• showed high reactivity toward deprotonated BT through second-order rate constant estimation. A byproduct analysis demonstrated that BT underwent hydroxylation and chlorine substitution, and a high yield of 1-chlorobenzotriazole (1-ClBT) formation was observed. Even though the sunlight/free chlorine process resulted in a low level of mineralization, no Microtox® toxicity was detected in the treated solutions. Briefly, the significant contribution of ClO• to BT removal under alkaline conditions implies that sunlight/free chlorine could be utilized in a broader range of treatment conditions.

Photoaged polystyrene microplastics serve as photosensitizers that enhance cimetidine photolysis in an aqueous environment.

Microplastics (MPs) have received much attention in recent years because of their continuous photoaging process in aquatic environments. However, little research has been conducted on the photochemistry of aged microplastics and the associated effects on coexisting pharmaceuticals. This study investigated the photodegradation of cimetidine via aged polystyrene microplastics (PS-MPs) with different aging times (0-7 d) under simulated sunlight irradiation (700 W/m2). PS-MPs with 5 d of aging time resulted in much faster cimetidine degradation (>99%) after 2 h of irradiation than pristine PS-MPs (<8%). The enhanced photodegradation of cimetidine by aged PS-MPs was related to the increase in chromophoric oxygenated groups (CO, C-O) followed by redshifted absorbance through the photoaging process, which induced the formation of the environmentally persistent free radicals (EPFRs) OH, 1O2 and 3PS*. However, only 1O2 and 3PS* contributed to enhanced cimetidine photodegradation, with 1O2 playing a more important role in our case. This work also demonstrated that other compounds that are susceptible to indirect photolysis, such as codeine and morphine, are likewise significantly degraded under irradiation in the presence of aged PS-MPs. Although previous studies have reported how MPs can increase the persistence of contaminants, this study demonstrates that MPs can serve as photosensitizers and alter the fate of coexisting pharmaceuticals in aquatic environments.

Intracellular organic matter from Chlorella vulgaris enhances the photodegradation of acetaminophen.

Algae is able to accelerate the photodegradation rate of contaminants under sunlight irradiation, and this process can be attributed to algal substances, namely, intracellular organic matter (IOM) and extracellular organic matter (EOM). This study aimed to investigate the efficiencies and mechanisms of the photodegradation of three pharmaceuticals - acetaminophen (ACE), codeine (COD) and cephradine (CFD) - in the presence of Chlorella vulgaris and its algal substances. The result shows that a much higher photodegradation rate of acetaminophen was obtained in the presence of IOM (kobs = 0.250 hr-1) than in the presence of EOM (kobs = 0.060 hr-1). The photodegradation mechanisms of acetaminophen were demonstrated and verified by scavenger experiments and probe tests. The major reactive species for acetaminophen photodegradation was triplet-state IOM (3IOM∗), which contributed 93.52% of the photodegradation, while ⋅OH was the secondary contributor (5.60%), with 1O2 contributing the least (0.88%). Chlorella vulgaris also effectively enhanced the photodegradation of codeine and cephradine. However, the photodegradation behaviors of codeine and cephradine in the presence of algal substances were different from those of acetaminophen, indicating that the photodegradation mechanisms might depend on the type of compound. This study not only demonstrates the effectiveness of algal substances in the photodegradation of acetaminophen, codeine and cephradine under sunlight irradiation but also provides a comprehensive study on the photodegradation mechanisms of acetaminophen in the presence of algal substances.

Detection of Recurrent Non-Hodgkin Lymphoma on In-111 Capromab Pendetide Imaging.

A 73-year-old man presented with a rising prostate-specific antigen (PSA) level 5 years following brachytherapy for prostate cancer. In-111 capromab pendetide (ProstaScint) whole-body planar imaging revealed abnormal uptake in the right knee, localizing to a mass in the popliteal fossa on SPECT/CT. MRI showed a mass encasing the popliteal artery and vein, subsequently found to be non-Hodgkin lymphoma on biopsy. Response of the mass to chemotherapy was documented on ¹8F-FDG PET/CT. Elevated In-111 capromab pendetide uptake in soft tissue can be important but unrelated to prostate cancer, as demonstrated in this case.

TiO2 photocatalytic degradation and transformation of oxazaphosphorine drugs in an aqueous environment.

This study investigated the TiO2 photocatalytic degradation and transformation of the oxazaphosphorines ifosfamide (IFO), cyclophosphamide (CP) and trofosfamide (TRO). Under the optimum conditions of TiO2=100mg/L, IFO=100µg/L and solution pH=5.5, IFO was completely removed within 10min (k=0.433min(-1)). The results indicated that OHfree radicals generated by valence holes in the bulk solution were the predominant species for the degradation of IFO. At higher initial concentrations of oxazaphosphorines (20mg/L), >50% of TOC remained after 6h of reaction time, indicating that parent compounds were transformed to byproducts, which exhibit higher Microtox acute toxicities; chlorinated byproducts were likely the source of toxicity. Photocatalytic degradation pathways of the three oxazaphosphorines were proposed. IFO, CP and TRO follow very similar pathways and bond-breaking processes: ketonization and breaking of the CCl bond, the PN bond and the CN bond (N-dechloroethylation). Chloride (Cl(-)) release is likely the first and primary step in the decomposition process. Several of the identified byproducts were also metabolites, which implies that photocatalytic oxidation proceeds through pathways that are similar to metabolic pathways.

Photocatalytic oxidation of 5-fluorouracil and cyclophosphamide via UV/TiO2 in an aqueous environment.

Cytostatic drugs are a class of pharmaceuticals that are increasingly used in cancer therapies; 5-fluorouracil is one of the most commonly used cytostatic (antineoplastic) drugs in the world. This study applied photocatalytic oxidation to remove 5-fluorouracil. Degussa P25 showed a higher photocatalytic degradation efficiency for 5-fluorouracil removal than Aldrich TiO2 and ZnO. Under optimal conditions (20 mg L(-1) TiO2 at pH 5.8), 200 µg L(-1) 5-fluorouracil can be removed within 2 h (k = 0.0375 min(-1)). 5-fluorouracil was found to be decomposed by near-surface OH free radicals produced from valence holes (hvb(+)). At a relatively high concentration, 5-fluorouracil (27.6 mg L(-1)) is >99.9% removed within 4 h by 300 mg L(-1) Degussa P25, while 24 h is required to reach complete mineralization with 96.7% fluoride recovery. Cyclophosphamide is another widely used cancer drug that follows a similar decomposition pathway. Cyclophosphamide (27.6 mg L(-1)) was also >99.9% eliminated within 4 h, but dechlorination and mineralization reached only 79.9% and 55.1%, respectively, after 16 h of irradiation. Together with the results for Microtox(®), it is suggested that the oxidation products of cyclophosphamide are even more recalcitrant and toxic. For engineering practices, despite the fact that photocatalytic oxidation can rapidly remove target antineoplastic, it is also important to further evaluate the treatment efficiency of the photoproducts.

Fate of selected pharmaceuticals and personal care products after secondary wastewater treatment processes in Taiwan.

Pharmaceuticals and personal care products (PPCPs) constitute a class of chemicals of emerging concern due to the potential risks they pose to organisms and the environment, even at low concentrations (ng/L). Recent studies have found that PPCPs are not efficiently removed in secondary wastewater treatment plants (WWTPs). This study has: (1) simultaneously investigated the occurrence of sixty-one PPCPs using solid phase extraction and high-performance liquid chromatography-tandem mass spectrometry, (2) evaluated removal efficiencies of target PPCPs in six WWTPs that discharge effluents into major Taiwanese rivers, and lastly (3) examined matrix interference during analysis of target PPCPs in water samples. The twenty target PPCPs were chosen for their high detection frequencies, high influent concentrations, and stability during wastewater treatment processes. Caffeine and acetaminophen were detected at the highest concentrations (as high as 24,467 and 33,400 ng/L) and were effectively removed (both >96%); other PPCPs were detected in the high ng/L range but were not effectively removed. Matrix interference (by ion suppression or enhancement) during the analysis resulted in underestimation of the removal efficiencies of erythromycin-H(2)O, cefazolin, clarithromycin, ibuprofen, diclofenac, clofibric acid and gemfibrozil.

Emergency joint aspiration: a guide for radiologists on call.

Septic arthritis is a disabling and possibly life-threatening disease that requires early diagnosis for optimal management. It is important that clinical and imaging features of septic arthritis be promptly identified. In addition, because other disease entities may have characteristics similar to those of septic arthritis, analysis of a needle biopsy specimen may be necessary for differential diagnosis. Radiologists may be asked to perform emergent aspiration of a possibly infected joint. It is important that those who perform aspiration procedures be familiar with a safe and effective imaging-guided arthrocentesis technique that is tailored to the individual patient and the specific joint affected.

Lateral meniscus root tear and meniscus extrusion with anterior cruciate ligament tear.

PURPOSE: To retrospectively determine the prevalence of posterior lateral meniscus root tears (LMRTs), as depicted on magnetic resonance (MR) images, in patients with an anterior cruciate ligament (ACL) tear and to investigate the association of LMRTs with lateral meniscus extrusion and other ligament injuries. MATERIALS AND METHODS: Institutional review board approval was obtained; informed consent was not required. This study was HIPAA compliant. MR images were obtained in 174 male and 119 female patients (mean age, 37 years; age range, 16-87 years) and retrospectively reviewed for LMRT, medial meniscus root tear (MMRT), nonroot meniscus tear, meniscus extrusion, and presence of meniscofemoral ligaments (MFLs). The chi2 and unpaired Student t tests were performed. RESULTS: In 33 patients, 34 meniscus root tears were identified. An LMRT was present in 26 (9.8%) of 264 patients, and an MMRT was present in eight (3.0%) (P=.008). Lateral meniscus extrusion was present in six (23%) of 26 LMRTs and five (2.2%) of 231 patients with normal meniscus roots (P<.001). Complex or deep radial tears were found in three of five cases of lateral meniscus extrusion and normal root. The MFL was not observed in five (19%) of 26 studies of an LMRT. Among these 26 studies of an LMRT, lateral meniscus extrusion was identified in three (14%) of 21 cases in which the MFL was intact and in three (60%) of five cases in which the MFL was not identified (P<.03). Prevalence of an extruded meniscus was seven (88%) of eight for an MMRT and six (23%) of 26 for an LMRT (P=.001). CONCLUSION: Prevalence of LMRTs is greater than that of MMRTs in patients with an ACL tear. LMRTs and complex and radial tears are associated with lateral meniscus extrusion; an absent MFL is more prevalent in patients with LMRTs and when the meniscus is extruded.

The use of phage display technique for the isolation of androgen receptor interacting peptides with (F/W)XXL(F/W) and FXXLY new signature motifs.

Early studies suggested that the signature motif, LXXLL, within steroid hormone receptor p160 coregulators may play important roles for the mediation of receptor-coregulator interaction. Interestingly, several androgen receptor (AR) coregulators, such as ARA70 and ARA55, may not use such a unique motif to mediate their coregulator activity. Here we apply the phage display technique to identify some new signature motifs, (F/W)XXL(F/W) and FXXLY (where F is phenylalanine, W is tryptophan, L is leucine, Y is tyrosine, and X is any amino acid) that can influence the interaction between AR and AR coregulators. Sequence analyses found that several AR coregulators, such as ARA70, ARA55, ARA54, and FHL2, contain FXXL(F/Y) motifs. Both glutathione S-transferase pull-down assays and transient transfection reporter assays demonstrate that these AR coregulators may use the FXXL(F/Y) motif to interact with AR and exert their AR coregulator activity. Exchanging the amino acid of Phe, Trp, or Tyr in this newly identified signature motif cluster may influence these peptides to interact with AR. The motif-containing peptides, as well as ARA70 or ARA54, may require selective flanking sequences for the better interaction with AR. In addition to influencing the AR transactivation, these motifs in AR-interacting peptides/proteins were also able to influence the AR N-/C-terminal interaction. Together, our data suggest that AR interacting peptides and/or AR coregulators may utilize the (F/W)XXL(F/W) and FXXLY motifs to mediate their interaction with AR and exert their influences on the AR transactivation.

Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues.

By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice.