Pilot randomized sham-controlled trial of self-acupressure to manage the symptom cluster of insomnia, depression, and anxiety in cancer patients undergoing chemotherapy.

PURPOSE: Current evidence for using self-acupressure to manage the cancer-related symptom cluster of insomnia, depression, and anxiety, while promising, is unknown. This study evaluated the feasibility of self-acupressure to manage this symptom cluster and to explore its potential effectiveness. METHODS: Participants were assigned randomly to three study groups, namely the true acupressure (TAP), the sham acupressure (SAP), and the enhanced standard care group (ESC). Participants in the TAP and SAP groups received a training session on acupressure and were required to practice self-acupressure at home once per day for 28 days. The duration of participant involvement was 8 weeks. Patients completed a Numerical Rating Scale (NRS) for each symptom, the Insomnia Severity Index, the Hospital Anxiety and Depression Scale, and the Functional Assessment of Cancer Therapy-General at baseline (T1), post-intervention (T2, week 4), and post follow-up (T3, week 8). RESULTS: The results indicated that the intervention had clinical significance in improving the targeted symptoms and quality of life. In the TAP group, the symptom cluster severity was significantly lower than in the other groups at T2 (p < 0.05). The insomnia severity and anxiety scores in the TAP and SAP groups were significantly lower than those in ESC at T2 and T3 (p < 0.05). CONCLUSION: The trial was feasible. The promising results of the study suggest that further testing of self-acupressure is warranted to inform its effectiveness on the targeted symptom cluster in patients with cancer. A placebo effect was evident alongside therapeutic effects. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT03823456) on January 30th, 2019.

Risk Factors and Protective Immunity Against Rabies in Unvaccinated Butchers Working at Dog Slaughterhouses in Northern Vietnam.

Vietnam is a rabies-endemic country where eating dog meat is customary. However, the risks of rabies transmission to dog slaughtering and processing workers have not been identified. This study aimed to determine the rabies neutralizing antibody (NTA) and risk factors in dog slaughterers to propose appropriate intervention methods for this occupational group. In 2016, a cross-sectional study on NTA against rabies virus and related factors was conducted among 406 professional dog slaughterers in Vietnam. The participants were interviewed using a structured questionnaire, and their sera were tested for rabies NTA by a rapid focus fluorescence inhibition test. Statistical algorithms were used to analyze the data. The results showed that most of the professional dog butchers (344/406 subjects, 84.7%) had no rabies NTA. Interestingly, 7.8% (29/373) had NTA without a rabies vaccination history. Over 5 years of experience as a dog butcher was positively associated with the presence of NTA in unvaccinated individuals (OR = 6.16, P = 0.001). The NTA in vaccinated butchers was present in higher titer and for longer persistence to those of other previously reported professionals, which is possibly as a result of multiple exposures to low levels of rabies virus antigens during dog slaughtering. Our study demonstrated that professional dog butchers in Vietnam are at a high risk of rabies virus infection, apart from those with common bite experiences. In countries where dog meat consumption is customary, rabies control and prevention activities should focus on safety during dog trading and slaughtering.

Rabies-infected dogs at slaughterhouses: A potential risk of rabies transmission via dog trading and butchering activities in Vietnam.

The study aimed to determine the status of neutralizing antibodies and rabies virus infection in dogs at slaughterhouses in Hanoi city from 2015 to 2017. A total of 2,376 pairs of blood and brain samples were collected from dogs at 92 slaughterhouses (8 large slaughterhouses and 84 small slaughterhouses) in 6 districts in Hanoi. Of the 1,500 dog samples from the large slaughterhouses where imported dogs were slaughtered, no dog brain samples were infected with rabies virus and no blood samples were positive for rabies neutralizing antibodies. Meanwhile, 7/876 (0.8%) of dog brain samples from small slaughterhouses in which slaughtered local dogs were positive for rabies virus and 26.4% had neutralizing antibodies against rabies virus. Analysis of the genetic characteristics of these rabies viruses showed that they all had a common origin with the domestic strains circulating in Northern Vietnam. Research results suggested that there was a potential risk of rabies transmission to humans through dog slaughtering activities in Vietnam. Vaccination for dogs should be strengthened, strictly implemented and frequently monitored to reach the rate of herd vaccination coverage as WHO's recommendation. Dog trading and slaughtering activities should be strictly monitored to minimize the risk of rabies transmission to humans.

Synthesis and anti-HIV evaluation of hybrid-type prodrugs conjugating HIV integrase inhibitors with d4t by self-cleavable spacers containing an amino acid residue.

In an attempt to combine the anti-HIV inhibitory capacity of reverse transcriptase (RT) inhibitors (NRTIs) and integrase (IN) inhibitors (INIs), several heterodimer analogues of the previously reported [d4T]-PABC-[INI] and [d4T]-OABC-[INI] prototypes have been prepared. In these novel series, we wished to extend our results to conjugates which incorporated an enzymatically labile aminoacid unit (L-alanine) connected to d4T through a self-immolative para- or ortho-aminobenzyl carbonate (PABC or OABC) spacer. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable to that of the [L-708,906]-PABC-[d4T] Heterodimer A prototype. However, although the compounds proved inhibitory to HIV-1, they were less potent than the parent compounds from which they were derived.

Synthesis of prodrug-type anti-HIV agents conjugating a REVERSE transcriptase inhibitor to a HIV-1 integrase inhibitor by a spontaneously cleavable linker.

Based on the prodrug concept as well as the combination of two different classes of anti-HIV agents, we have designed and synthesized a series of anti-HIV double-drugs consisting of a nucleoside reverse transcriptase inhibitor (NRTI) conjugated with an integrase inhibitor (INI) through a spontaneously cleavable linker in an effort to enhance the antiviral activity. These conjugates combined in their structure a dideoxy-didehydro-nucleoside (ddN) such as d4T and an INI such as alpha, gamma-diketo acid (DKA) analogues of L-708,906 and L-731,988 linked through an appropriate self-immolative spacer. Among these novel bis-substrate inhibitors, several conjugates exhibited antiviral activity but this effect was accompanied for some of them by an increased cytotoxicity by comparison to d4T, DKA or even some precursors. These compounds are nevertheless interesting candidates for further investigations.