Gentamicin (Gm) is an aminoglycoside commonly used to treat bacterial infections such as tularemia – the disease caused by Francisella tularensis. In addition to being pathogenic, F. tularensis is found in environmental niches such as soil where this bacterium likely encounters Gm producers (Micromonospora sp.). Here we show that F. tularensis exhibits increased resistance to Gm at ambient temperature (26°C) compared to mammalian body temperature (37°C). To evaluate whether F. tularensis was less permeable to Gm at 26°C, a fluorescent marker [Texas Red (Tr)] was conjugated with Gm, yielding Tr-Gm. Bacteria incubated at 26°C showed reduced fluorescence compared to those at 37°C when exposed to Tr-Gm suggesting that uptake of Gm was reduced at 26°C. Unconjugated Gm competitively inhibited uptake of Tr-Gm, demonstrating that this fluorescent compound was taken up similarly to unconjugated Gm. Lysates of F. tularensis bacteria incubated with Gm at 37°C inhibited the growth of Escherichia coli significantly more than lysates from bacteria incubated at 26°C, further indicating reduced uptake at this lower temperature. Other facultative pathogens (Listeria monocytogenes and Klebsiella pneumoniae) exhibited increased resistance to Gm at 26°C suggesting that the results generated using F. tularensis may be generalizable to diverse bacteria. Regulation of the uptake of antibiotics provides a mechanism by which facultative pathogens survive alongside antibiotic-producing microbes in nature.

Futility disputes are more likely to be resolved-and relational breaches repaired-by engaging in a process that fosters communication between clinicians, patients, and families. This essay calls for mediative fluency. The preemptive use of a futility definition can stifle conversation when it is needed most, exacerbating the very power imbalances and associated health disparities that often precipitate futility disputes. When clinicians, patients, and families engage in dialogue, clinicians can appreciate what motivates requests for what is thought to be futile care, and patients and families can better understand the limits of available therapies. This sharing of knowledge, values, and attitudes cannot be achieved through the unilateral invocation of a futility definition. Furthermore, futility definitions are prone to interpretative judgment by clinicians and can be informed by the norms and attitudes attendant to a practitioner's medical specialty. They also need to be interpreted in the context of emerging trends in medical therapeutics and in relation to the clinical details of each case. In the aggregate, these challenges make the application of a futility definition futile.

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Several socio-cultural factors complicate mental health care in the ultra-Orthodox Jewish population. These include societal stigma, fear of the influence of secular ideas, the need for rabbinic approval of the method and provider, and the notion that excessive concern with the self is counter-productive to religious growth. Little is known about how the religious beliefs of this population might be employed in therapeutic contexts. One potential point of convergence is the Jewish philosophical tradition of introspection as a means toward personal, interpersonal, and spiritual growth. We reviewed Jewish religious-philosophical writings on introspection from antiquity (the Babylonian Talmud) to the Middle Ages (Duties of the Heart), the eighteenth century (Path of the Just), the early Hasidic movement (the Tanya), and modernity (Alei Shur, Halakhic Man). Analysis of these texts indicates that: (1) introspection can be a religiously acceptable reaction to existential distress; (2) introspection might promote alignment of religious beliefs with emotions, intellect and behavior; (3) some religious philosophers were concerned about the demotivating effects of excessive introspection and self-critique on religious devotion and emotional well-being; (4) certain religious forms of introspection are remarkably analogous to modern methods of psychiatry and psychology, particularly psychodynamic psychotherapy and cognitive-behavioral therapy. We conclude that homology between religious philosophy of emotion and secular methods of psychiatry and psychotherapy may inform the choice and method of mental health care, foster the therapist-patient relationship, and thereby enable therapeutic convergence.