Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission.

In the absence of a prophylactic vaccine, the use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition by uninfected individuals is a promising approach to slowing the epidemic, but its efficacy is hampered by incomplete patient adherence and ART-resistant variants. Here, we report that competitive inhibition of HIV Env-CCR5 binding via the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of CCR5-tropic SHIVSF162P3. Injection of Leronlimab weekly at 10 mg/kg provides significant but partial protection, while biweekly 50 mg/kg provides complete protection from SHIV acquisition. Tissue biopsies from protected macaques post challenge show complete CCR5 receptor occupancy and an absence of viral nucleic acids. After Leronlimab washout, protected macaques remain aviremic, and adoptive transfer of hematologic cells into naïve macaques does not transmit viral infection. These data identify CCR5 blockade with Leronlimab as a promising approach to HIV prophylaxis and support initiation of clinical trials.

Hiding in plain sight - platelets, the silent carriers of HIV-1.

There are approximately 38 million people globally living with Human immunodeficiency virus 1 (HIV-1) and given the tremendous success of combination antiretroviral therapy (cART) this has dramatically reduced mortality and morbidity with prevention benefits. However, HIV-1 persists during cART within the human body and re-appears upon cART interruption. This HIV-1 reservoir remains a barrier to cure with cellular sites of viral persistence not fully understood. In this study we provide evidence corroborating a recently published article in STM demonstrating the role of platelets as a novel cellular disseminator of HIV-1 particles in the setting of viral suppression. Using classical transmission electron microscopy with and without immunogold labeling, we visualize HIV-1 in both platelets and monocytes in cART suppressed HIV donors. Our study suggests that due to the close proximity of platelets and monocytes an alternative life cycle of HIV-1 cycling within monocytes and platelets without the need of active replication under cART occurs. Our findings are supported by the lack of detectable HIV-1 particles in platelets derived from HIV uninfected donors or the 'Berlin' patient suggesting that platelets may serve as an underappreciated hidden bearer for HIV-1 and should be considered in HIV remission studies and trials.

Testing the adaptive advantage of a threatened species over an invasive species using a stochastic population model.

Introduced species are a major threat to freshwater biodiversity. Often eradication is not feasible, and management must focus on reducing impacts on native wildlife. This requires an understanding of how native species are affected but also how environmental characteristics influence population dynamics of both invasive and native species. Such insights can inform how to manipulate systems in order to take advantage of life-history traits native species possesses that invaders do not. The highly invasive fish, Gambusia holbrooki, has been implicated in the decline of many freshwater fish and amphibians. In south-eastern Australia, one of these is the threatened native fish, Galaxiella pusilla. As G. pusilla can survive periods without surface water, this presents an opportunity for adaptive management, given G. holbrooki lack these adaptations. We develop a stochastic population model to explore the impact of G. holbrooki on G. pusilla and test the feasibility of both natural and management-induced drying to protect this species. Our results support recent empirical studies showing G. holbrooki are a serious threat to G. pusilla persistence, especially through impacts on larval survival. While persistence is more likely in water bodies that frequently dry out, even optimal natural drying regimes may be insufficient when impacts from G. holbrooki are high. However, management-induced drying may allow persistence of G. pusilla in sites inhabited by both species. Given our model outcomes, the biology of these species and the habitats they occupy, we recommend maintaining or restoring aquatic and riparian vegetation and natural drying regimes to protect G. pusilla from G. holbrooki, in addition to undertaking management-induced drying of invaded water bodies. Our results provide insights into how the effects of G. holbrooki may be mitigated for other native species, which is important given this species is perhaps the most pervasive invader of freshwater ecosystems. We conclude with a discussion of the potential for using disturbance processes in the management of invasive species more broadly in freshwater and terrestrial systems.

Clinical documentation for patient care: models, concepts, and liability considerations for pharmacists.

PURPOSE: A guide to the appropriate documentation of the critical aspects of the patient medical record to ensure reimbursement and the reduction of medical liability is presented. SUMMARY: Several documentation styles can be adopted to record pharmacist interventions, including unstructured notes, semistructured notes, and systematic notes. Documentation should be clear, concise, legible, nonjudgmental, patient focused, and standardized, and it should ensure patient confidentiality. Systematic documentation styles include SOAP (subjective, objective, assessment, plan), TITRS (title, introduction, text, recommendation, signature), and FARM (findings, assessment, recommendations or resolutions, management). SOAP is the primary form for which payers traditionally reimburse. Systematic documentation should be used to demonstrate how pharmacist interventions improved patient care and should not just be used for reimbursement. Pharmacists have the opportunity to build a collaborative relationship with other professionals and with patients. Documentation can provide evidence of this symbiotic relationship where the pharmacist assists in providing a caring and compassionate environment for the patient's benefit. Professional liability, as it relates to clinical documentation, can be an issue. Documentation provides the necessary information to successfully manage the process of discovery and the review of the conduct of all parties involved in a liability issue. CONCLUSION: Documentation in a universal format allows for communication among health care practitioners. Written documentation is one key to a successful, open-communication partnership among providers. In addition, accurate, appropriate, and concise documentation is an essential component of ensuring that the patient care provided is evident, not only for patient safety and continuity but also for cases where reimbursement and quality of care are being challenged contractually or legally.

Results of four-corner arthrodesis using dorsal circular plate fixation.

PURPOSE: Four-corner arthrodesis with scaphoid excision has been used to reduce pain and preserve functional range of motion for patients with radioscaphoid arthritis. Early results of 4-corner arthrodesis with scaphoid excision using dorsal circular plate fixation are compared with reported results in the literature. METHODS: We reviewed retrospectively the first 18 four-corner arthrodeses performed with this system by 4 hand surgeons. Two patients had revision surgery for nonunions before the study that were considered failures. Eight patients returned for final radiographs, objective examination, and functional questionnaire. The average follow-up period was 20 months (range, 13-33 mo). These results were compared with reported results in the literature using alternate fixation methods. RESULTS: Radiographic union was achieved in only 3 wrists. Range of motion was 46% that of the opposite normal wrist and grip strength compared with the opposite wrist was 56%. Five patients would have the procedure again and 6 of 8 have returned to their original employment. CONCLUSIONS: Four-corner arthrodesis with scaphoid excision using a circular internal fixation plate produced a high number of nonunions. Grip strength and range of motion results also were inferior to those reported in the literature.

Direct regulation of RNA polymerase III transcription by RB, p53 and c-Myc.

The synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III is cell cycle regulated in higher organisms. Overexpression of pol III products is a general feature of transformed cells. These observations may be explained by the fact that a pol III-specific transcription factor, TFIIIB, is strongly regulated by the tumor suppressors RB and p53, as well as the proto-oncogene product c-Myc. RB and p53 repress TFIIIB, but this restraint can be lost in tumors through a variety of mechanisms. In contrast, c-Myc binds and activates TFIIIB, causing potent induction of pol III transcription. Using chromatin immunoprecipitation and RNA interference, we show that c-Myc interacts with tRNA and 5S rRNA genes in transformed cervical cells, stimulating their expression. Availability of pol III products may be an important determinant of a cell's capacity to grow. The ability to regulate pol III output may therefore be integral to the growth control functions of RB, p53 and c-Myc.

Adverse effects of temazepam in older adults with chronic insomnia.

BACKGROUND: Benzodiazepine-hypnotics are frequently used for treating insomnia in older adults; however, there is little information about adverse effects associated with their usage over several weeks, particularly in this segment of the population. OBJECTIVE: This study reports on the incidence of adverse effects of temazepam in older adults with chronic insomnia and examines whether the addition of cognitive-behaviour therapy (CBT) is associated with less drug used and fewer adverse effects. METHOD: Sixty patients with chronic and primary insomnia were randomized to temazepam (n = 20), placebo (n = 20) or temazepam plus CBT (n = 20). Data from the physicians' weekly assessments and patients' sleep diaries were used to evaluate adverse effects, the dose (7.5-30 mg) at which they occurred, and drug use patterns over the 8-week course of treatment. RESULTS: The incidence of adverse effects was infrequent, as shown by the low percentages of complaints reported by patients in the temazepam (7.8%), placebo (10.8%) and combination groups (8.3%). The severity of adverse events was mild and decreased over the course of treatment. The maximum dose was reached by 10 patients receiving temazepam, 14 placebo and 7 in the combined treatment. The average nightly dosage used was 20 mg for both the temazepam and placebo groups and 16 mg for the combined condition. Patients receiving temazepam plus CBT used less drugs, with approximately the same incidence of adverse effects. CONCLUSION: Temazepam is a safe hypnotic for use by older adults over an 8-week treatment period. There are few adverse effects and behavioural tolerance to those effects develop over time. The addition of cognitive-behavioural intervention reduced both the amount of medication used and the incidence of adverse effects, with comparable sleep improvements.