Smart diagnostics devices through artificial intelligence and mechanobiological approaches.

The present work illustrates the promising intervention of smart diagnostics devices through artificial intelligence (AI) and mechanobiological approaches in health care practices. The artificial intelligence and mechanobiological approaches in diagnostics widen the scope for point of care techniques for the timely revealing of diseases by understanding the biomechanical properties of the tissue of interest. Smart diagnostic device senses the physical parameters due to change in mechanical, biological, and luidic properties of the cells and to control these changes, supply the necessary drugs immediately using AI techniques. The latest techniques like sweat diagnostics to measure the overall health, Photoplethysmography (PPG) for real-time monitoring of pulse waveform by capturing the reflected signal due to blood pulsation), Micro-electromechanical systems (MEMS) and Nano-electromechanical systems (NEMS) smart devices to detect disease at its early stage, lab-on-chip and organ-on-chip technologies, Ambulatory Circadian Monitoring device (ACM), a wrist-worn device for Parkinson's disease have been discussed. The recent and futuristic smart diagnostics tool/techniques like emotion recognition by applying machine learning algorithms, atomic force microscopy that measures the fibrinogen and erythrocytes binding force, smartphone-based retinal image analyser system, image-based computational modeling for various neurological disorders, cardiovascular diseases, tuberculosis, predicting and preventing of Zika virus, optimal drugs and doses for HIV using AI, etc. have been reviewed. The objective of this review is to examine smart diagnostics devices based on artificial intelligence and mechanobiological approaches, with their medical applications in healthcare. This review determines that smart diagnostics devices have potential applications in healthcare, but more research work will be essential for prospective accomplishments of this technology.

Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs).

Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depending on the biological action studied. The SPRM asoprisnil is being studied in women with symptomatic uterine leiomyomata and endometriosis. Asoprisnil shows a high degree of uterine selectivity as compared to effects on ovulation or ovarian hormone secretion in humans. It induces amenorrhea and decreases leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. It also has endometrial antiproliferative effects. In pregnant animals, the myometrial, i.e. labor-inducing, effects of asoprisnil are blunted or absent. Studies in non-human primates played a key role during the preclinical development of selective progesterone receptor modulators. These studies provided the first evidence of uterus-selective effects of asoprisnil and structurally related compounds, and the rationale for clinical development of asoprisnil.

Selective progesterone receptor modulators (SPRMs): a novel therapeutic concept in endometriosis.

Endometriosis, the presence of endometrial tissue outside the uterus, is a progressive, estrogen-dependent disease and occurs nearly exclusively in menstruating women of reproductive age. Pain syndrome, however, represents the major clinical problem of this disease, manifested as dysmenorrhea, pelvic pain, lower abdominal pain, and dyspareunia. The manifestation of the disease, that is, the pain syndrome, rather than the disease itself currently represents the major indication for both the medical and surgical therapies of endometriosis. The major drawbacks of current medical therapies of endometriosis are sometimes severe side effects. In this review, selective progesterone receptor modulators (SPRMs, mesoprogestins) as a potential therapeutic concept in endometriosis are discussed. Due to endometrial selectivity and favorable pharmacological profile, SPRMs may have advantages over the current medical treatments of this disease. Other emerging therapeutic approaches for this disease are also mentioned.

Therapeutic potential for the selective progesterone receptor modulator asoprisnil in the treatment of leiomyomata.

Asoprisnil is a novel selective progesterone receptor modulator that exhibits partial agonist and antagonist activities in animals and humans. It demonstrates a high degree of progesterone receptor specificity and tissue selectivity. Although asoprisnil at high doses exhibited some antiglucocorticoid activity in animal models, no antiglucocorticoid effects were observed at therapeutic doses in humans. In male rats, asoprisnil showed mixed androgenic and antiandrogenic properties. Unlike antiprogestins, asoprisnil at high doses exhibited only marginal labor-inducing activity in guinea pigs during midpregnancy and was completely ineffective in inducing preterm parturition. In nonhuman primates, asoprisnil completely eliminated menstrual cyclicity and induced endometrial atrophy. Early clinical studies of asoprisnil in healthy volunteers demonstrated a dose-dependent suppression of menstruation, irrespective of the effects on ovulation, with no change in basal estrogen concentrations and no breakthrough bleeding. Phase 2 studies in subjects with uterine fibroids demonstrated that asoprisnil induced amenorrhea and reduced the volume of the dominant leiomyoma in a dose-dependent manner without altered basal estrogen and with virtually no clinical symptoms of estrogen deprivation. Asoprisnil seems to exhibit a direct inhibitory effect on both the endometrium and leiomyoma. In all studies to date, asoprisnil has maintained a favorable safety and tolerability profile. Thus, asoprisnil has the potential to target the major clinical symptoms of leiomyomata related to both menorrhagia and the size of the tumors and may, therefore, reduce or eliminate the need for surgery.

Asoprisnil (J867): a selective progesterone receptor modulator for gynecological therapy.

Asoprisnil is a novel selective steroid receptor modulator that shows unique pharmacodynamic effects in animal models and humans. Asoprisnil, its major metabolite J912, and structurally related compounds represent a new class of progesterone receptor (PR) ligands that exhibit partial agonist and antagonist activities in vivo. Asoprisnil demonstrates a high degree of receptor and tissue selectivity, with high-binding affinity for PR, moderate affinity for glucocorticoid receptor (GR), low affinity for androgen receptor (AR), and no binding affinity for estrogen or mineralocorticoid receptors. In the rabbit endometrium, both asoprisnil and J912 induce partial agonist and antagonist effects. Asoprisnil induces mucification of the guinea pig vagina and has pronounced anti-uterotrophic effects in normal and ovariectomized guinea pigs. Unlike antiprogestins, asoprisnil shows only marginal labor-inducing activity during mid-pregnancy and is completely ineffective in inducing preterm parturition in the guinea pig. Asoprisnil exhibits only marginal antiglucocorticoid activity in transactivation in vitro assays and animal models. In male rats, asoprisnil showed weak androgenic and anti-androgenic properties. In toxicological studies in female cynomolgus monkeys, asoprisnil treatment abolished menstrual cyclicity and endometrial atrophy. Early clinical studies of asoprisnil in normal volunteers demonstrated a dose-dependent suppression of menstruation irrespective of the effects on ovulation, with no change in basal estrogen concentrations and no antiglucocorticoid effects. Unlike progestins, asoprisnil does not induce breakthrough bleeding. With favorable safety and tolerability profiles thus far, asoprisnil appears promising as a novel treatment of gynecological disorders, such as uterine fibroids and endometriosis.

Lead poisoning associated with Ayurvedic drug presenting as intestinal obstruction: a case report.

INTRODUCTION: Lead poisoning is most commonly caused by occupational exposure. It presents with a myriad of signs and symptoms ranging from mild anemia to frank encephalopathy, depending on the blood lead levels as well as the duration of exposure. Intake of herbal/Ayurvedic medicine may also lead to plumbism as heavy metals are often incorporated in such medications with the belief that such metals have medicinal properties. METHODS: We report a case of lead poisoning caused by Ayurvedic medication. The patient presented with symptoms of intestinal obstruction to the surgical casualty. RESULTS: The patient presented with symptoms that mimicked intestinal obstruction. No specific etiology could be determined. Serum lead levels were determined and diagnosis of lead poisoning ascertained. The lead content of the medicine was analyzed and it contained 30% w/w lead. CONCLUSIONS: The diagnosis of heavy metal poisoning consequent to intake of alternative medicine must be kept in mind when a patient presents with vague complaints.

Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial.

BACKGROUND AND AIM: Hepatorenal syndrome (HRS) occurs in about 18% of cirrhotic patients with ascites and is characterized by intense renal vasoconstriction, low glomerular filtration rate and preserved tubular function and normal renal histology. The aim of the present study was to examine the effects of terlipressin on renal function, systemic hemodynamics and clinical outcome in patients with HRS. METHODS: The study was a randomized controlled single-blind trial. We randomly assigned 24 consecutive patients with HRS to treatment with terlipressin 1 mg i.v. at 12-h intervals (group A; n = 12) or placebo at 12-h intervals (group B; n = 12). The end-point of the study was improvement in renal functions defined as reversal of HRS and survival at 15 days. RESULTS: The two groups were comparable at baseline. After treatment with terlipressin, urine output significantly (P < 0.05) increased progressively in group A (day 4, 960 +/- 40 mL/24 h; day 8, 1068 +/- 56 mL/24 h) compared with group B (day 4, 451 +/- 40 mL/24 h; day 8, 291 +/- 45 mL/24 h). Creatinine clearance improved (P < 0.05) in group A (day 4, 20.2 +/- 2.1 mL/min; day 8, 35 +/- 2.8 mL/min) compared with group B (day 4, 11.3 +/- 1.3 mL/min; day 8, 9.3 +/- 1.7 mL/min). Serum creatinine decreased in group A but not in group B (day 8, 1.6 +/- 0.01 compared with 3.9 +/- 0.26, P < 0.05). Mean arterial pressure increased significantly (P < 0.05) in group A. Terlipressin administration was associated with transient self-limiting side-effects including crampy abdominal pain in two patients and cardiac arrhythmias in three patients. Five of the 12 patients survived in group A compared with none in group B at day 15 (P < 0.05) and all survivors had reversal of HRS. CONCLUSION: In patients with HRS, terlipressin significantly improved renal functions and systemic hemodynamics, and showed a trend towards better clinical outcome. The drug merits further evaluation with different dosages and longer schedules.