Aims It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). Methods and results This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17–3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03–4.57, P = 0.041). The mortality rates were similar between the renin–angiotensin–aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28–2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45–0.94, P = 0.20). Conclusion While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.

A new experimental approach was developed to measure the concentration of charged functional groups (FGs) in the active layer of thin-film composite reverse osmosis (RO) and nanofiltration (NF) membranes as a function of solution pH. FT30 RO membrane, with a fully aromatic polyamide (PA) active layer sandwiched between a polysulfone support and a coating layer, was used. The experiments consisted of saturating charged FGs with heavy ion probes, and determining the ion probe concentration by Rutherford backscattering spectrometry (RBS). Deprotonated carboxylic groups were saturated with Ag+, and protonated amine groups with W04(2-). The ionization behavior of carboxylic and amine groups was modeled based on acid-base equilibrium theory. While the ionization behavior of amine groups was satisfactorily described by one dissociation constant (pKa = 4.74), two pKa values (5.23 and 8.97) were necessary to describe the titration curve of carboxylic groups. These results were consistent with the bimodal pore size distribution (PSD) of FT30 active layer reported in the literature. The calculated total concentrations of carboxylic and amine groups in the active layer of the FT30 RO membrane studied were 0.432 and 0.036 M, respectively, and the isoelectric point (IEP) was 4.7. The total concentration of carboxylic and amine groups revealed that the degree of cross-linking of the PA active layer of the FT30 RO membrane studied was 94%.

Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage.

Itch is relieved by scratching, but the neural mechanisms that are responsible for this are unknown. Spinothalamic tract (STT) neurons respond to itch-producing agents and transmit pruritic information to the brain. We observed that scratching the cutaneous receptive field of primate STT neurons produced inhibition during histamine-evoked activity but not during spontaneous activity or activity evoked by a painful stimulus, suggesting that scratching inhibits the transmission of itch in the spinal cord in a state-dependent manner.Itch is an unpleasant sensation that is associated with the desire to scratch. For most itches, relief is obtained by scratching in or around the region of itchy skin. However, itch that is coincident with skin disease or systemic disorders can be severe. In these circumstances, the desire to scratch is often overwhelming, but incessant scratching is harmful and leads to itch-scratch cycles that damage the skin and exacerbate the problem 1 . The mechanism by which scratching sup-presses itch is unknown. However, it has been hypothesized that this mechanism occurs in the CNS because noxious counterstimuli (for example, scratching) reduce itch when delivered many centimeters away from the site of itching and itch does not develop in a zone of cutaneous centrally mediated allodynia 2-5. Histamine-sensitive dorsal horn neurons with unidentified projections are variably depressed by counterstimuli in rats6; however, unlike monkeys7, rats do not scratch in response to histamine, complicating the interpretation of these data with regard to itch.In humans, anterolateral cordotomy eliminates the perception of itch from contralateral body sites below the lesion, implicating the STT in the transmission of pruritic information to the brain 8 . STT neurons can be activated for many minutes following the cutaneous application of itch-producing agents such as histamine 9-11 , matching the sensation of itch in humans 12 . Therefore, we examined whether the responses to histamine in primate STT neurons could be inhibited by scratching in the receptive field. STT neurons were recorded in the lumbar dorsal horn and were identified by antidromic stimulation (Supplementary Methods and Supplementary Fig. 1 Every neuron tested had a mechanically sensitive receptive field and was excited by scratching (n = 28). Repeated scratches to the receptive field of single STT neurons reliably evoked similar discharges (Fig. 1). Two-thirds of STT neurons showed an after-discharge following scratching (Fig. 1b).Histamine (20 μg in 10 μL) was then injected intradermally into the receptive field. In eight neurons that responded to histamine ( Supplementary Fig. 2 online), the receptive field was scratched for 10 s during the response. Each histamine-responsive neuron showed fewer action potentials during the 10-s period immediately following the scratch than during the 10-s period before the scratch (Fig. 2). Most neurons increased their discharge during scratching, but two cells appeared to reduce their discharge ...

Itch of peripheral origin requires information transfer from the spinal cord to the brain for perception. Here, primate spinothalamic tract (STT) neurons from lumbar spinal cord were functionally characterized by in vivo electrophysiology to determine the role of these cells in the transmission of pruriceptive information. One hundred eleven STT neurons were identified by antidromic stimulation and then recorded while histamine and cowhage (a nonhistaminergic pruritogen) were sequentially applied to the cutaneous receptive field of each cell. Twenty percent of STT neurons responded to histamine, 13% responded to cowhage, and 2% responded to both. All pruriceptive STT neurons were mechanically sensitive and additionally responded to heat, intradermal capsaicin, or both. STT neurons located in the superficial dorsal horn responded with greater discharge and longer duration to pruritogens than STT neurons located in the deep dorsal horn. Pruriceptive STT neurons discharged in a bursting pattern in response to the activating pruritogen and to capsaicin. Microantidromic mapping was used to determine the zone of termination for pruriceptive STT axons within the thalamus. Axons from histamine-responsive and cowhage-responsive STT neurons terminated in several thalamic nuclei including the ventral posterior lateral, ventral posterior inferior, and posterior nuclei. Axons from cowhage-responsive neurons were additionally found to terminate in the suprageniculate and medial geniculate nuclei. Histamine-responsive STT neurons were sensitized to gentle stroking of the receptive field after the response to histamine, suggesting a spinal mechanism for alloknesis. The results show that pruriceptive information is encoded by polymodal STT neurons in histaminergic or nonhistaminergic pathways and transmitted to the ventrobasal complex and posterior thalamus in primates.