Effect of Cold vs Temperate Conditions on Physical Performance During Extended Mountain Warfare Training at Moderate Altitude.

INTRODUCTION: The purpose of this study was to investigate the effect of environmental conditions on body composition, upper body power, and lower body power throughout a ∼4-week military mountain training exercise. We hypothesized that countermovement jump and ballistic push-up performance would decrease as a result of extended mountain field training and that winter (cold) conditions would result in greater decrements compared to fall (temperate) conditions. We also expected to observe a strong positive correlation between changes in performance and changes in skeletal muscle mass. Finally, we expected acute changes in performance upon altitude exposure. MATERIALS AND METHODS: A total of 111 U.S. Infantry Marines (110 M; 1 F) provided written informed consent to participate in this study according to a protocol approved by the Naval Health Research Center. There were 54 participants in the fall cohort and 57 in the winter cohort. Maximum effort countermovement jump and ballistic push-up performance were assessed at different timepoints: (1) baseline at the sea level, (2) before training at ∼2100 m, (3) midpoint of training at ∼2100 m, (4) end of training at ∼2100 m, and (5) after 3 to 4 weeks of recovery at the sea level. The fall cohort trained at moderate temperatures (average day/night, 20°C/3°C), whereas the winter cohort trained under snowy winter conditions (7°C/-14°C). RESULTS: The results suggested that seasonal conditions did not significantly affect changes in body composition or physical performance. Furthermore, no acute effects of altitude on physical performance were detected. Training exercise did, however, cause performance decrements in countermovement jump height, countermovement jump peak power, and ballistic push-up height. Repeated measure correlation analyses suggested that there was a weak positive correlation between the decrease in skeletal muscle mass and the decrease in countermovement jump peak power throughout the training. CONCLUSIONS: The results of our study suggest that explosive movements are negatively affected by extended military training, seemingly independent of environmental training conditions or temperature. Planning and execution of military training should account for the likelihood that warfighter physical power will decline and may not return to pretraining levels within the month following the training event. It may also be advised to consider targeted exercises to aid in recovery of muscular strength and power. Future work should consider additional factors that likely influenced the decrease in physical performance that occurs during extended military training, such as nutrition, sleep, and psychological and cognitive stresses.

Treatment-Refractory, Castration-Resistant Prostate Cancer With Liver Metastasis: A Promising Modality of Therapy.

Although significant advances in the treatment of prostate cancer (PC) have recently been made, the treatment of metastatic liver disease remains challenging. Recent advances have led to multiple novel therapies and multi-treatment approaches combining systemic and locoregional modalities, such as thermal ablation, representing a promising strategy that has received attention in recent years. Nevertheless, no standard locoregional treatment regimens exist for the management of liver metastases of PC. In addition, regional therapy alone is unlikely to provide durable cancer control. Here, we report for the first time a successful treatment of hepatic metastases of PC using stereotactic image-guided percutaneous microwave ablation and the poly (ADP-ribose) polymerase-1 inhibitor, olaparib.

Allowable room temperature excursions for refrigerated medications: A 20-year review.

PURPOSE: The aim of this review was to build upon previous literature describing the maximum duration for which refrigerated medications can tolerate room temperature excursions while maintaining stability and potency. METHODS: During a 12-month period ending in June 2021, the prescribing information and published monographs from multiple pharmacy compendia were reviewed for all medications and biologic products approved by the US Food and Drug Administration (FDA) for human use since January 2000. Products that were subsequently withdrawn from the US market were excluded. When temperature excursion data was unavailable in published form, product manufacturers were surveyed via telephone and/or email. Acceptable storage information for all products for which storage is recommended at temperatures below room temperature (20-25 °C [68-77 °F]) was compiled and arranged in tabular format. RESULTS: Of the 705 products or formulations approved by FDA during the predefined time period, 246 were identified as requiring storage at temperatures below room temperature. After review of available prescribing information and manufacturer communications, if applicable, acceptable periods of excursion to temperatures at room temperature or higher were identified for 214 products (87%). CONCLUSION: Information related to acceptable periods of room temperature excursion was compiled for a total of 214 products approved for US distribution since 2000. The included tables may increase patient safety and decrease medication loss or related expenditures.

Successful use of immunotherapy to treat advanced cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a multisystem inherited disorder associated with fragile skin, blister formation and poor wound healing. Patients with RDEB are at significantly increased risk of recurrent and aggressive cutaneous squamous cell carcinoma (cSCC) and because of their disease complexity, conventional therapies may not be possible. Recent advances in cancer immunotherapy have led to the successful use of immune checkpoint inhibitors (ICIs) in melanoma and other malignancies. However, the effects of ICIs in patients with cSCC and RDEB are currently unknown. A 30-year-old woman with RDEB and multiple unresectable cSCCs was found to have high tumour mutational burden and PD-L1 (programmed cell death-ligand 1) expression. She was started on an ICI, which yielded disease control and was well tolerated. Furthermore, her RDEB wounds improved. This case demonstrates successful use of immunotherapy for advanced cSCC in RDEB, a disease that is often challenging to treat with local therapies.

Phototheranostic nanoplatform based on a single cyanine dye for image-guided combinatorial phototherapy.

This study represents a novel phototheranostic nanoplatform based on the near-infrared (NIR) heptamethine cyanine dye, IR775, which is capable of concurrent real-time fluorescence imaging and cancer eradication with combinatorial phototherapy. To achieve water solubility and enhance tumor delivery, the hydrophobic IR775 dye was loaded into a biocompatible polymeric nanoparticle with a diameter of ~40nm and slightly negative surface charge (-2.34mV). The nanoparticle-encapsulated hydrophobic IR775 dye (IR775-NP) is characterized by an enhanced fluorescence quantum yield (16%) when compared to the water soluble analogs such as ICG (2.7%) and IR783 (8%). Furthermore, the developed IR-775-NP efficiently generates both heat and reactive oxygen species under NIR light irradiation, eradicating cancer cells in vitro. Finally, animal studies revealed that the IR775-NP accumulates in cancer tumors after systemic administration, efficiently delineates them with NIR fluorescence signal and completely eradicates chemo resistant cancer tissue after a single dose of combinatorial phototherapy.

Dendrimer-encapsulated naphthalocyanine as a single agent-based theranostic nanoplatform for near-infrared fluorescence imaging and combinatorial anticancer phototherapy.

Multifunctional theranostic platforms capable of concurrent near-infrared (NIR) fluorescence imaging and phototherapies are strongly desired for cancer diagnosis and treatment. However, the integration of separate imaging and therapeutic components into nanocarriers results in complex theranostic systems with limited translational potential. A single agent-based theranostic nanoplatform, therefore, was developed for concurrent NIR fluorescence imaging and combinatorial phototherapy with dual photodynamic (PDT) and photothermal (PTT) therapeutic mechanisms. The transformation of a substituted silicon naphthalocyanine (SiNc) into a biocompatible nanoplatform (SiNc-NP) was achieved by SiNc encapsulation into the hydrophobic interior of a generation 5 polypropylenimine dendrimer following surface modification with polyethylene glycol. Encapsulation provides aqueous solubility to SiNc and preserves its NIR fluorescence, PDT and PTT properties. Moreover, an impressive photostability in the dendrimer-encapsulated SiNc has been detected. Under NIR irradiation (785 nm, 1.3 W cm(-2)), SiNc-NP manifested robust heat generation capability (ΔT = 40 °C) and efficiently produced reactive oxygen species essential for PTT and PDT, respectively, without releasing SiNc from the nanopaltform. By varying the laser power density from 0.3 W cm(-2) to 1.3 W cm(-2) the therapeutic mechanism of SiNc-NP could be switched from PDT to combinatorial PDT-PTT treatment. In vitro and in vivo studies confirmed that phototherapy mediated by SiNc can efficiently destroy chemotherapy resistant ovarian cancer cells. Remarkably, solid tumors treated with a single dose of SiNc-NP combined with NIR irradiation were completely eradicated without cancer recurrence. Finally, the efficiency of SiNc-NP as an NIR imaging agent was confirmed by recording the strong fluorescence signal in the tumor, which was not photobleached during the phototherapeutic procedure.

Hepatitis C virus core protein leads to immune suppression and liver damage in a transgenic murine model.

Hepatitis C virus (HCV) is remarkably efficient in establishing persistent infection, possibly mediated by an impaired immune response to HCV infection. There is compelling evidence that HCV can infect immune cells, such as macrophages, B cells, and T cells. It has been previously reported that HCV core, the first protein expressed during the early phase of viral infection, contains the immunomodulatory function of suppressing host immune responses. This altered function of immune cells caused by HCV infection may explain the ineffective immune response to HCV. To further characterize the immunomodulatory role of HCV core in vivo, we generated transgenic (TG) mice by directing the expression of core protein to T lymphocytes by using the CD2 promoter. T-lymphocyte responses, including the production of gamma interferon and interleukin-2, were significantly diminished in these mice compared to their non-TG littermates. The inhibition of T-lymphocyte responsiveness may be due to the increased susceptibility of peripheral T lymphocytes to Fas-mediated apoptosis. Surprisingly, significant lymphocyte infiltration was observed in the portal tracts of livers isolated from core TG mice, associated with increasing serum alanine aminotransferase levels. Moreover, no intrahepatic lymphocytes or liver damage was found in non-TG littermates and core TG mice bred to Fas-deficient lpr mice. These results suggest that HCV core drives liver injury by increasing Fas-mediated apoptosis and liver infiltration of peripheral T cells.