What drives disagreement about moral hypocrisy? Perceived comparability and how people exploit it to criticize enemies and defend allies.

Charges of hypocrisy are usually thought to be to be damning. Yet when a hypocrisy charge is made, there often remains disagreement about whether or not its target really is a hypocrite. Why? Three pre-registered experiments (N = 2599) conceptualize and test the role of perceived comparability in evaluating hypocrisy. Calling someone a hypocrite typically entails invoking a comparison-one meant to highlight internal contradiction and cast moral character into question. Yet there is ambiguity about which sorts of comparisons are valid in the first place. We argue that disagreements about moral hypocrisy often boil down to disagreements about comparability. Although the comparability of two situations should not depend on whose behavior is being scrutinized, observers shift comparability judgments in line with social motives to criticize or defend. In short, we identify a cognitive factor that can help to explain why, for similar patterns of behavior, people see hypocrisy in their enemies but consistency in themselves and their allies.

COVID-19 activity risk calculator as a gamified public health intervention tool.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted over 200 countries leading to hospitalizations and deaths of millions of people. Public health interventions, such as risk estimators, can reduce the spread of pandemics and epidemics through influencing behavior, which impacts risk of exposure and infection. Current publicly available COVID-19 risk estimation tools have had variable effectiveness during the pandemic due to their dependency on rapidly evolving factors such as community transmission levels and variants. There has also been confusion surrounding certain personal protective strategies such as risk reduction by mask-wearing and vaccination. In order to create a simple easy-to-use tool for estimating different individual risks associated with carrying out daily-life activity, we developed COVID-19 Activity Risk Calculator (CovARC). CovARC is a gamified public health intervention as users can "play with" how different risks associated with COVID-19 can change depending on several different factors when carrying out routine daily activities. Empowering the public to make informed, data-driven decisions about safely engaging in activities may help to reduce COVID-19 levels in the community. In this study, we demonstrate a streamlined, scalable and accurate COVID-19 risk calculation system. Our study also demonstrates the quantitative impact of vaccination and mask-wearing during periods of high case counts. Validation of this impact could inform and support policy decisions regarding case thresholds for mask mandates, and other public health interventions.

Treatment of Bolivian Leishmania braziliensis Cutaneous and Mucosal Leishmaniasis.

Although infection with Leishmania braziliensis is perhaps the key reason to treat New World cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML), the total literature contains relatively few reported cases. With the aim of supplementing the meager clinical information available, we searched the records of Jorochito (Dermatology) Hospital, Bolivia, for the years 1999-2020 and identified treatment records for 1,696 naive CL patients and 355 naive ML patients. Because follow-up was poor for this real-world treatment experience in the developing world, only 255 CL patients (15%) and 114 ML patients (32%) attended follow-up at Hospital. We therefore engaged in an Active Search for "lost" patients, located a further 542 CL patients (32%) and 142 ML patients (44%), thus eventually accomplished follow up on 697 CL patients (41%) and 256 ML patients (72%). Granular adverse event data derived from hospital records is listed for the 902 CL and 86 ML patients administered Glucantime intramuscularly, the 401 CL and 202 ML patients administered Glucantime intravenously, and the 163 CL and 89 ML patients administered miltefosine orally. Efficacy was obtained from hospital records for patients seen at hospital and from patient recall communicated by telephone for the patients found in the Active Search. The overall CL cure rate was 508 of 697 CL patients (73%) with follow-up: intramuscular Glucantime-196/293 (67%); intravenous Glucantime-90/126 (71%); intralesional Glucantime-34/54 (63%); oral miltefosine-52/69 (75%). The overall ML cure rate was 161 of 256 ML patients (63%) with follow-up: intramuscular Glucantime-26/48 (54%); intravenous Glucantime-66/104 (63%); intravenous amphotericin B deoxycholate-19/35 (54%); oral miltefosine-50/71 (70%). We offer this extensive adverse event and efficacy experience as useful guides for clinicians presented with a L. braziliensis infection. The cure rates also illustrate the quandary of New World CL and ML chemotherapy: sufficiently high to be useful but nevertheless needing augmentation with new agents.

Reflecting on identity change facilitates confession of past misdeeds.

[Correction Notice: An Erratum for this article was reported online in Journal of Experimental Psychology: General on Feb 24 2022 (see record 2022-33834-001). In the article "Reflecting on Identity Change Facilitates Confession of Past Misdeeds" by Beth Anne Helgason and Jonathan Zev Berman (Journal of Experimental Psychology: General. Advance online publication. January 31, 2022. http://dx.doi.org/10.1037/xge0001180), the labels of several confidence intervals were omitted due to a copyediting error.] Across four studies (N = 3,351), we demonstrate that reflecting on identity change increases confession and decreases justification of past misdeeds. Moreover, publicly communicating one's identity change to others increases confession above and beyond privately reflecting on identity change. By severing their connection with their past self, individuals can admit to past a misdeed ("I did it") while reducing their fear that doing so will implicate their present moral character ("But that's not who I am anymore"). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

An estrogen (17α-ethinyl estradiol-3-sulfate) reduces mortality in a swine model of multiple injuries and hemorrhagic shock.

BACKGROUND: Although 17α-ethinyl estradiol-3-sulfate (EES) reduces mortality in animal models of controlled hemorrhage, its role in a clinically relevant injury model is unknown. We assessed the impact of EES in a swine model of multiple injuries and hemorrhage. METHODS: The study was performed under Good Laboratory Practice, with 30 male uncastrated swine (25-50 kg) subjected to tibial fracture, pulmonary contusion, and 30% controlled hemorrhage for an hour. Animals were randomized to one of five EES doses: 0 (control), 0.3, 1, 3, and 5 mg/kg, administered postinjury. Subjects received no resuscitation and were observed for 6 hours or until death. Survival data were analyzed using Cox-proportional hazard regression. Left ventricular pressure-volume loops were used to derive preload recruitable stroke work as a measure of cardiac inotropy. Immediate postinjury preload recruitable stroke work values were compared with values at 1 hour post-drug administration. RESULTS: Six-hour survival for the 0, 0.3, 1, 3, and 5 mg/kg groups was 0%, 50%, 33.3%, 16.7%, and 0%, respectively. Following Cox regression, the hazard (95% confidence interval) of death was significantly reduced in the 0.3 (0.22 [0.05-0.93]) and 1 (0.24 [0.06-0.89]) mg/kg groups but not the 3 (0.49 [0.15-1.64]) and 5 (0.46 [0.14-1.47]) mg/kg groups. Mean survival time was significantly extended in the 1 mg/kg group (246 minutes) versus the 0 mg/kg group (96 minutes) (p = 0.04, t test). At 1 hour post-drug administration, inotropy was significantly higher than postinjury values in the 0.3 and 1 mg/kg groups (p = 0.003 and p < 0.001, respectively). Inotropy was unchanged in the 3 and 5 mg/kg groups but significantly depressed in the control (p = 0.022). CONCLUSION: Administration of EES even in the absence of fluid resuscitation reduces mortality and improves cardiac inotropy in a clinically relevant swine model of multiple injuries and hemorrhage. These findings support the need for a clinical trial in human trauma patients.

Prosocial behavior and reputation: When does doing good lead to looking good?

One reason people engage in prosocial behavior is to reap the reputational benefits associated with being seen as generous. Yet, there isn't a direct connection between doing good deeds and being seen as a good person. Prosocial actors are often met with suspicion and sometimes castigated as disingenuous braggarts, empty virtue-signalers, or holier-than-thou hypocrites. In this article, we review recent research on how people evaluate those who engage in prosocial behavior and identify key factors that influence whether observers will praise or denigrate a prosocial actor for doing a good deed.

Mechanisms and consequences of casein kinase II and ankyrin-3 regulation of the epithelial Na+ channel.

Activity of the Epithelial Na+ Channel (ENaC) in the distal nephron fine-tunes renal sodium excretion. Appropriate sodium excretion is a key factor in the regulation of blood pressure. Consequently, abnormalities in ENaC function can cause hypertension. Casein Kinase II (CKII) phosphorylates ENaC. The CKII phosphorylation site in ENaC resides within a canonical "anchor" ankyrin binding motif. CKII-dependent phosphorylation of ENaC is necessary and sufficient to increase channel activity and is thought to influence channel trafficking in a manner that increases activity. We test here the hypothesis that phosphorylation of ENaC by CKII within an anchor motif is necessary for ankyrin-3 (Ank-3) regulation of the channel, which is required for normal channel locale and function, and the proper regulation of renal sodium excretion. This was addressed using a fluorescence imaging strategy combining total internal reflection fluorescence (TIRF) microscopy with fluorescence recovery after photobleaching (FRAP) to quantify ENaC expression in the plasma membrane in living cells; and electrophysiology to quantify ENaC activity in split-open collecting ducts from principal cell-specific Ank-3 knockout mice. Sodium excretion studies also were performed in parallel in this knockout mouse. In addition, we substituted a key serine residue in the consensus CKII site in ß-ENaC with alanine to abrogate phosphorylation and disrupt the anchor motif. Findings show that disrupting CKII signaling decreases ENaC activity by decreasing expression in the plasma membrane. In the principal cell-specific Ank-3 KO mouse, ENaC activity and sodium excretion were significantly decreased and increased, respectively. These results are consistent with CKII phosphorylation of ENaC functioning as a "switch" that favors Ank-3 binding to increase channel activity.

Case Report: COVID-19 Misdiagnosed as a Drug Reaction to Miltefosine.

We present case reports of two patients treated with miltefosine for mucocutaneous leishmaniasis whose gastrointestinal symptoms were initially diagnosed as a drug reaction and only later recognized as due to COVID-19. Gastrointestinal symptoms of COVID-19 are unusual, whereas gastrointestinal adverse drug reactions are very common. These reports exemplify that this infrequent presentation of COVID-19 is likely to be ascribed to a more common etiology such as a gastrointestinal drug reaction.

Moral Choice When Harming Is Unavoidable.

Past research suggests that actors often seek to minimize harm at the cost of maximizing social welfare. However, this prior research has confounded a desire to minimize the negative impact caused by one's actions (harm aversion) with a desire to avoid causing any harm whatsoever (harm avoidance). Across six studies (N = 2,152), we demonstrate that these two motives are distinct. When decision-makers can completely avoid committing a harmful act, they strongly prefer to do so. However, harming cannot always be avoided. Often, decision-makers must choose between committing less harm for less benefit and committing more harm for more benefit. In these cases, harm aversion diminishes substantially, and decision-makers become increasingly willing to commit greater harm to obtain greater benefits. Thus, value trade-offs that decision-makers refuse to accept when it is possible to completely avoid committing harm can suddenly become desirable when some harm must be committed.

Liddle's syndrome mechanisms, diagnosis and management.

Liddle's syndrome is a genetic disorder characterized by hypertension with hypokalemic metabolic alkalosis, hyporeninemia and suppressed aldosterone secretion that often appears early in life. It results from inappropriately elevated sodium reabsorption in the distal nephron. Liddle's syndrome is caused by mutations to subunits of the Epithelial Sodium Channel (ENaC). Among other mechanisms, such mutations typically prevent ubiquitination of these subunits, slowing the rate at which they are internalized from the membrane, resulting in an elevation of channel activity. A minority of Liddle's syndrome mutations, though, result in a complementary effect that also elevates activity by increasing the probability that ENaC channels within the membrane are open. Potassium-sparing diuretics such as amiloride and triamterene reduce ENaC activity, and in combination with a reduced sodium diet can restore normotension and electrolyte imbalance in Liddle's syndrome patients and animal models. Liddle's syndrome can be diagnosed clinically by phenotype and confirmed through genetic testing. This review examines the clinical features of Liddle's syndrome, the differential diagnosis of Liddle's syndrome and differentiation from other genetic diseases with similar phenotype, and what is currently known about the population-level prevalence of Liddle's syndrome. This review gives special focus to the molecular mechanisms of Liddle's syndrome.

Mass Drug Administration of Triclabendazole for Fasciola Hepatica in Bolivia.

Human infection with Fasciola hepatica leads to obstruction of the common bile duct by adult worms and disease characterized by biliary colic, epigastric pain, and nausea. Recommended treatment is a single dose of triclabendazole (TCBZ) (10 mg/kg). Because in the 1990s the Bolivian Altiplano bordering Lake Titicaca was thought to have the highest prevalence of human fascioliasis worldwide, the Bolivian Ministry of Health instituted TCBZ mass drug administration (MDA). From 2008 to 2016 (excepting 2015), one dose of 250 mg was administered, usually in September/October, to each resident of highly endemic regions willing to participate. This is apparently the first reported use of MDA for Fasciola. The proportion of persons in key regions receiving TCBZ MDA was 87% in 2016. In 2017, we resurveyed key regions, and found that the MDA program had been dramatically successful. Whereas Fasciola prevalence was reported as 26.9% in Huacullani/Tiahuanaco and 12.6% in Batallas in 1999, there was 0.7% prevalence in Huacullani/Tiahuanaco and 1% in Batallas in 2017. However, lessons from schistosomiasis control efforts suggest that for sustained control of Fasciola infection, Fasciola MDA needs to be maintained and coupled with measures to control infection in the intermediary snail and in the animal hosts of F. hepatica.

Approval of Tafenoquine for Malaria Chemoprophylaxis.

Malaria chemoprophylaxis has become increasingly prominent now that it is used for vulnerable populations in endemic regions in addition to nonimmune travelers to those regions. The objective would be a drug with > 95% efficacy and that is easily tolerated, including in children and pregnant women. For individuals who prefer weekly rather than daily drug administration, a further objective is a product that is administered weekly. The deficiencies of present agents are parasite resistance to chloroquine, neuropsychiatric liability of mefloquine, the need for daily dosing for atovaquone-proguanil, and daily dosing plus adverse reactions for doxycycline. A primaquine analogue, tafenoquine, has a 17-day half-life and was approved for weekly prophylaxis in the United States and in Australia in 2018. Weekly tafenoquine was equal to mefloquine in efficacy in nonimmunes. The tafenoquine label contains a contraindication for preexisting psychosis, but not for the broad number of other neuropsychiatric disorders which are listed as contraindications in the mefloquine label. As an 8-aminoquinoline, tafenoquine is contraindicated for glucose-6-phosphate dehydrogenase (G6PD)-deficient persons or in pregnancy if the fetus might be G6PD deficient. Other possible significant adverse reactions for tafenoquine are declines in hemoglobin levels reported in some G6PD-normal patients, asymptomatic elevations in methemoglobin, and minor psychiatric events. The lack of broad neuropsychiatric adverse reactions suggests that tafenoquine may have a role as the weekly prophylactic of choice for G6PD-normal persons.

Topical 15% Paromomycin-Aquaphilic for Bolivian Leishmania braziliensis Cutaneous Leishmaniasis: A Randomized, Placebo-controlled Trial.

BACKGROUND: Cutaneous leishmaniasis (CL) presents as 1 or more skin lesions, which makes local therapy inherently attractive compared to systemic therapy that exposes the whole body to a drug. For 30 years, 15% paromomycin topical formulations have been in clinical experimentation. Recently, 15% paromomycin in Aquaphilic, a complex base to facilitate adsorption into the lesion, was found superior to aquaphilic vehicle for Old World Leishmania major disease. METHODS: We performed a randomized trial of 15% paromomycin in Aquaphilic (40 patients) vs Aquaphilic vehicle (20 patients) vs a positive control (intralesional pentamidine; 20 patients) against L. braziliensis CL in Bolivia. RESULTS: Cure rates after 6 months of follow-up were 31 of 40 (77.5%, 95% confidence interval [CI] 62.5-88%) for paromomycin-Aquaphilic, 2 of 20 (10%, 95% CI 3-30%) for Aquaphilic vehicle (P < .0001 vs paromomycin-Aquaphilic), and 14 of 20 (70%, 95% CI 48-85.5%) for intralesional pentamidine. Both paromomycin-Aquaphilic and the Aquaphilic vehicle were very well tolerated, with only grade 1 adverse reactions in 5-10% of patients. CONCLUSIONS: Against L. braziliensis CL, a prevalent, aggressive form of New World CL, 15% paromomycin-aquaphilic was vastly superior to a negative vehicle control and was comparable in efficacy to a positive control. This study enlarges the potential use of 15% paromomycin-Aquaphilic from one form of Old World CL to CL more generally. CLINICAL TRIALS REGISTRATION: NCT03096457.