Acknowledging the use of human cadaveric tissues in research papers: Recommendations from anatomical journal editors

Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors‐in‐chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.     

Neural connectivity between the hypothalamic supramammillary nucleus and appetite‐ and motivation‐related regions of the rat brain

The supramammillary nucleus (SuM) has an emerging role in appetite control. We have shown that the rat SuM is activated during hunger or food anticipation, or by ghrelin administration. In the present study, we characterised the connectivity between the SuM and key appetite‐ and motivation‐related nuclei in the rat. In adult wild‐type rats, or rats expressing Cre recombinase under the control of the tyrosine hydroxylase (TH) promoter (TH‐Cre rats), we used c‐Fos immunohistochemistry to visualise and correlate the activation of medial SuM (SuMM) with activation in the lateral hypothalamic area (LH), the dorsomedial hypothalamus (DMH) or the ventral tegmental area (VTA) after voluntary consumption of a high‐sugar, high‐fat food. To determine neuroanatomical connectivity, we used retrograde and anterograde tracing methods to specifically investigate the neuronal inputs and outputs of the SuMM. After consumption of the food there were positive correlations between c‐Fos expression in the SuMM and the LH, DMH and VTA (P = 0.0001, 0.01 and 0.004). Using Fluoro‐Ruby as a retrograde tracer, we demonstrate the existence of inputs from the LH, DMH, VTA and ventromedial hypothalamus (VMH) to the SuMM. The SuMM showed reciprocal inputs to the LH and DMH, and we identified a TH‐positive output from SuMM to DMH. We co‐labelled retrogradely‐labelled sections for TH in the VMH, or for TH, orexin and melanin‐concentrating hormone in the LH and DMH. However, we did not observe any colocalisation of immunoreactivity with any retrogradely‐labelled cells. Viral mapping in TH‐Cre rats confirms the existence of a reciprocal SuMM‐DMH connection and shows that TH‐positive cells project from the SuMM and VTA to the lateral septal area and cingulate cortex, respectively. These data provide evidence for the connectivity of the SuMM to brain regions involved in appetite control, and form the foundation for functional and behavioural studies aiming to further characterise the brain circuitry controlling eating behaviours.     

Association between hereditary predisposition to common cancers and congenital multimalformations

In a previous article we reported that mutations favoring cancer at adulthood seemed to improve fertility and limit miscarriages. Because spontaneous abortion may result from anomalies in embryo, we questioned if an increased frequency of congenital malformation could be evidenced among cancer-prone families. Oncogenetics database (≈193 000 members) of the comprehensive cancer center Jean Perrin was crossed with regional registry of congenital malformations (≈10 000). Among children born between 1986 and 2011, 176 children with malformation matched in both databases. In breast/ovaries cancer-prone families, the risk for malformations was multiplied by 2.4 [1.2-4.5] in case of a BRCA1 mutation. Frequencies of malformation in BRCA2 and MMR mutated families were similar to families without a cancer syndrome. In comparison to malformations concerning a unique anatomical system, multimalformations were significantly more frequent in case of BRCA or MMR mutations: compared to families without cancer syndrome, the risk of multimalformations was multiplied by 4.1 [0.8-21.7] for cancer-prone families but with no known deleterious mutation, by 6.9 [1.2-38.6] in families with a known mutation but an unknown parental mutational status and by 10.4 [2.3-46.0] when one parent carried the familial mutation. No association with the type of anatomical system was found, nor with multiple births. These results suggest that BRCA and MMR genes play an important role in human embryogenesis and that if their function is lowered because of heterozygote mutations, congenital malformations are either more likely (BRCA1 mutations) and/or more susceptible to concern several anatomical systems.     

What Does Diabetes “Taste” Like?

The T1R2 (taste type 1 receptor, member 2)/T1R3 (taste type 1 receptor, member 3) sweet taste receptor is expressed in taste buds on the tongue, where it allows the detection of energy-rich carbohydrates of food. This single receptor responds to all compounds perceived as sweet by humans, including natural sugars and natural and artificial sweeteners. Importantly, the T1R2/T1R3 sweet taste receptor is also expressed in extra-oral tissues, including the stomach, pancreas, gut, liver, and brain. Although its physiological role remains to be established in numerous organs, T1R2/T1R3 is suspected to be involved in the regulation of metabolic processes, such as sugar sensing, glucose homeostasis, and satiety hormone release. In this review, the physiological role of the sweet taste receptor in taste perception and metabolic regulation is discussed by focusing on dysfunctions leading to diabetes. Current knowledge of T1R2/T1R3 inhibitors making this receptor a promising therapeutic target for the treatment of type 2 diabetes is also summarized and discussed.     

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

Extended spectrum of antibiotic susceptibility for tuberculosis,Djibouti

In the Horn of Africa, there is a high prevalence of tuberculosis that is reported to be partly driven by multidrug-resistant (MDR) Mycobacterium tuberculosis strictu sensu strains. We conducted a prospective study to investigate M. tuberculosis complex species causing tuberculosis in Djibouti, and their in vitro susceptibility to standard anti-tuberculous antibiotics in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. Among the 118 mycobacteria isolates from 118 successive patients with suspected pulmonary tuberculosis, 111 strains of M. tuberculosis, five Mycobacterium canettii, one ‘Mycobacterium simulans’ and one Mycobacterium kansasii were identified. Drug-susceptibility tests performed on the first 78 isolates yielded nine MDR M. tuberculosis isolates. All isolates were fully susceptible to clofazimine, minocycline and chloramphenicol, and 75 of 78 isolates were susceptible to sulfadiazine. In the Horn of Africa, patients with confirmed pulmonary tuberculosis caused by an in vitro susceptible strain may benefit from anti-leprosy drugs, sulfamides and phenicol antibiotics.     

State insurance mandates and off‐label use of chemotherapy

Access to cancer drugs used off‐label is important to cancer patients but may drive up healthcare costs with little evidence of clinical benefit. We hypothesized that state health insurance mandates for private insurers to provide coverage for off‐label use of cancer drugs cause higher rates of off‐label use. We used Truven MarketScan data from 1999 to 2007 on utilization of 35 infused chemotherapy drugs in private health plans in the United States, covering the period when eight states implemented off‐label coverage laws. We studied trends in off‐label use of drugs, distinguishing between appropriate and inappropriate off‐label use according to drug compendia, and estimated difference‐in‐difference regressions of the effect of state laws on off‐label use. We estimate 41% of utilization was off‐label, including 17% of use conservatively defined as inappropriate. Trends show gradual declines in off‐label use over time. We also find no discernable effect of state laws mandating coverage of off‐label use of cancer drugs on utilization patterns under multiple empirical specifications. Our conclusion is that policymakers should consider shifting away from mandating coverage as a way to ensure access to drugs off‐label and towards incentivizing adherence to clinical practice guidelines to improve the quality and value of off‐label use.