Global Warming and Endocrinology: The Hyderabad Declaration of the South Asian Federation of Endocrine Societies.

Global warming and endocrine disorders are intertwined issues posing significant challenges. Greenhouse gases emanating from human activities drive global warming, leading to temperature rise and altered weather patterns. South Asia has experienced a noticeable temperature surge over the past century. The sizable population residing in the region heightens the susceptibility to the impact of global warming. In addition to affecting agriculture, water resources, and livelihood, environmental changes interfere with endocrine functioning. Resulting lifestyle changes increase the risk of metabolic and endocrine disorders. Individuals with diabetes face heightened vulnerability to extreme weather due to impaired thermoregulation. A high ambient temperature predisposes to heat-related illnesses, infertility, and nephropathy. Additionally, essential endocrine drugs and medical devices are susceptible to temperature fluctuations. The South Asian Federation of Endocrine Societies (SAFES) calls for collaboration among stakeholders to combat climate change and promote healthy living. Comprehensive approaches, including the establishment of sustainable food systems, promotion of physical activity, and raising awareness about environmental impacts, are imperative. SAFES recommends strategies such as prioritizing plant-based diets, reducing meat consumption, optimizing medical device usage, and enhancing accessibility to endocrine care. Raising awareness and educating caregivers and people living with diabetes on necessary precautions during extreme weather conditions are paramount. The heat sensitivity of insulin, blood glucose monitoring devices, and insulin pumps necessitates proper storage and consideration of environmental conditions for optimal efficacy. The inter-connectedness of global warming and endocrine disorders underscores the necessity of international collaboration guided by national endocrine societies. SAFES urges all stakeholders to actively implement sustainable practices to improve endocrine health in the face of climate change.

In-situ multicore fibre-based pH mapping through obstacles in integrated microfluidic devices.

Microfluidic systems with integrated sensors are ideal platforms to study and emulate processes such as complex multiphase flow and reactive transport in porous media, numerical modeling of bulk systems in medicine, and in engineering. Existing commercial optical fibre sensing systems used in integrated microfluidic devices are based on single-core fibres, limiting the spatial resolution in parameter measurements in such application scenarios. Here, we propose a multicore fibre-based pH system for in-situ pH mapping with tens of micrometer spatial resolution in microfluidic devices. The demonstration uses custom laser-manufactured glass microfluidic devices (called further micromodels) consisting of two round ports. The micromodels comprise two lintels for the injection of various pH buffers and an outlet. The two-port system facilitates the injection of various pH solutions using independent pressure pumps. The multicore fibre imaging system provides spatial information about the pH environment from the intensity distribution of fluorescence emission from the sensor attached to the fibre end facet, making use of the cores in the fibre as independent measurement channels. As proof-of-concept, we performed pH measurements in micromodels through obstacles (glass and rock beads), showing that the particle features can be clearly distinguishable from the intensity distribution from the fibre sensor.

Cross-talk between AMP-activated protein kinase and the sonic hedgehog pathway in the high-fat diet triggered colorectal cancer.

The major cause of colorectal cancer (CRC) related mortality is due to its metastasis. Signaling pathways play a definite role in the development and progression of CRC. Recent studies demonstrate that the regulation of the sonic hedgehog (Shh) pathway is beneficial in the CRC treatment strategy. Also, 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a well-known regulator of metabolism and inflammation, making it a suitable treatment option for CRC. Consumption of a high-fat diet (HFD) is a significant cause of CRC genesis. Also, the lipids play an indispensable role in aberrant activation of the Shh pathway. This review explains in detail the interconnection between HFD consumption, Shh pathway activation, and the progression of CRC. According to recent studies and literature, AMPK is a potential regulator that can control the complexities of CRC and reduce lipid levels and may directly inhibit shh signalling. The review also suggests the possible risk elements of AMPK activation in CRC due to its context-dependent role. Also, the activation of AMPK in HFD-induced CRC may modulate cancer progression by regulating the Shh pathway and metabolism.

Diagnosis and Management Considerations in Steroid-Related Hyperglycemia in COVID-19: A Position Statement from the Endocrine Society of India.

The current coronavirus disease (COVID-19) pandemic is showing no signs of abatement and result in significant morbidity and mortality in the infected patients. Many therapeutic agents ranging widely between antivirals and anti-inflammatory drugs have been used to mitigate the disease burden. In the deluge of the drugs being used for COVID-19 infection, glucocorticoids (GCs) stand out by reducing mortality amongst in-hospital severe-to-critically ill patients. Health-care practitioners have seen this as a glimmer of hope and started using these drugs more frequently than ever in clinical practice. The fear of mortality in the short term has overridden the concern of adverse long-term consequences with steroid use. The ease of availability, low cost, and apparent clinical improvement in the short term have led to the unscrupulous use of the steroids even in mild COVID-19 patients including self-medication with steroids. The use of GCs has led to the increasing incidence of hyperglycemia and consequent acute complications of diabetic ketoacidosis and mucormycosis in COVID-19 patients. There is an urgent need to dissipate information about optimum management of hyperglycemia during steroid use. In view of this, the Endocrine Society of India has formulated this position statement about the diagnosis and management of hyperglycemia due to the use of GCs in patients with COVID-19 infection.

Ultrafast laser ablation of a multicore polymer optical fiber for multipoint light emission.

We demonstrate the use of ultrafast laser pulses to precisely ablate the side of polymer multicore optical fibres (MCF) in such a way that light is efficiently coupled out of a set of MCF cores to free space. By individually exciting sets of MCF cores, this flexible "micro-window" technology allows the controllable generation of light sources at multiple independently selectable locations along the MCF. We found that the maximum fraction of light that could be side coupled from the MCF varied between 55% and 73%.

S1PR1 signaling in cancer: A current perspective.

Sphingosine-1-phosphate receptor 1 (S1PR1) is a G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P). S1PR1 belongs to the sphingosine-1-phosphate receptor subfamily comprising five members (S1PR1-5). It has prominent roles in regulating endothelial cell cytoskeletal structure, cell migration, immunomodulation, vasculogenesis during embryogenesis, T cell egress and Multiple sclerosis. This review is addressing the role of S1PR1 in tumorigenesis and therapeutic opportunities to target S1PR1 in cancer.

Mission Aware Motion Planning (MAP) Framework With Physical and Geographical Constraints for a Swarm of Mobile Stations.

In this paper, we propose a mission aware motion planning (MAP) framework for a swarm of autonomous unmanned ground vehicles (UGVs) or mobile stations in an uncertain environment for efficient supply of resources/services to unmanned aerial vehicles (UAVs) performing a specific mission. The MAP framework consists of two levels, namely, centralized mission planning and decentralized motion planning. On the first level, the centralized mission planning algorithm estimates the density of UAV in a given environment for determining the number of UGVs and their initial operating location. In the subsequent level, a decentralized motion planning algorithm which provides a closed-form expression for velocity command using adaptive density estimation has been proposed. Further, the physical and geographical constraints are integrated into motion planning. A Monte-Carlo simulation is performed to evaluate the advantages of the MAP over distributed stationary stations (DSSs) often used in the literature. The obtained results clearly indicate that in comparison with DSS, MAP reduces the average distance traveled by UAVs about 20%, reduces the loss of mission time by 90 s per interruption and power loss by 3 dB.

State-recycling and time-resolved imaging in topological photonic lattices.

Photonic lattices-arrays of optical waveguides-are powerful platforms for simulating a range of phenomena, including topological phases. While probing dynamics is possible in these systems, by reinterpreting the propagation direction as time, accessing long timescales constitutes a severe experimental challenge. Here, we overcome this limitation by placing the photonic lattice in a cavity, which allows the optical state to evolve through the lattice multiple times. The accompanying detection method, which exploits a multi-pixel single-photon detector array, offers quasi-real time-resolved measurements after each round trip. We apply the state-recycling scheme to intriguing photonic lattices emulating Dirac fermions and Floquet topological phases. We also realise a synthetic pulsed electric field, which can be used to drive transport within photonic lattices. This work opens an exciting route towards the detection of long timescale effects in engineered photonic lattices and the realisation of hybrid analogue-digital simulators.

Corrigendum: Sphingosine 1-Phosphate: A Novel Target for Lung Disorders.

[This corrects the article DOI: 10.3389/fimmu.2017.00296.].

The Origin and Functions of Exosomes in Cancer.

Exosomes are nanovesicles having a maximum size of 150 nm and is a newly emerging focus in various fields of research. Its role in cargo trafficking along with its differential expression is associated with the disrupted homeostasis and provides an opportunity to defend against different diseases like cancer. Furthermore, exosomes are rich in cargos, which contain proteins and nucleic acids that directly reflect the metabolic state of the cells from which it originates. This review summarizes recent studies on tumor-derived exosomes with an overview about biogenesis, their functions and potential of using as diagnostic and prognostic markers. We also discussed the current challenges and microfluidic-based detection approaches that might improve the detection of exosomes in different settings. More intricate studies of the molecular mechanisms in angiogenesis, pre-metastatic niche formation, and metastasis can give more promising insights and novel strategies in oncotherapeutics.

Targeting oncogenic transcription factors by polyphenols: A novel approach for cancer therapy.

Inflammation is one of the major causative factor of cancer and chronic inflammation is involved in all the major steps of cancer initiation, progression metastasis and drug resistance. The molecular mechanism of inflammation driven cancer is the complex interplay between oncogenic and tumor suppressive transcription factors which include FOXM1, NF-kB, STAT3, Wnt/ß- Catenin, HIF-1α, NRF2, androgen and estrogen receptors. Several products derived from natural sources modulate the expression and activity of multiple transcription factors in various tumor models as evident from studies conducted in cell lines, pre-clinical models and clinical samples. Further combination of these natural products along with currently approved cancer therapies added an additional advantage and they considered as promising targets for prevention and treatment of inflammation and cancer. In this review we discuss the application of multi-targeting natural products by analyzing the literature and future directions for their plausible applications in drug discovery.

Vagus Nerve Stimulation Modulates Complexity of Heart Rate Variability Differently during Sleep and Wakefulness.

Progressive loss of heart rate variability (HRV) and complexity are associated with increased risk of mortality in patients with cardiovascular disease and are a candidate marker for patients at risk of sudden cardiac death. HRV is influenced by the cardiac autonomic nervous system (ANS), although it is unclear which arm of the ANS (sympathetic or parasympathetic) needs to be perturbed to increase the complexity of HRV. In this case-control study, we have analyzed the relation between modulation of vagus nerve stimulation (VNS) and changes in complexity of HRV as a function of states of vigilance. We hypothesize that VNS - being a preferential activator of the parasympathetic system - will decrease the heart rate (HR) and increase the complexity of HRV maximum during sleep. The electrocardiogram (EKG) obtained from a 37-year-old, right-handed male with known intractable partial epilepsy and left therapeutic VNS was analyzed during wakefulness and sleep with VNS ON and OFF states. Age-matched control EKG was obtained from five participants (three with intractable epilepsy and two without epilepsy) that had no VNS implant. The study demonstrated the following: (1) VNS increased the complexity of HRV during sleep and decreased it during wakefulness. (2) An increase in parasympathetic tone is associated with increased complexity of HRV even in the presence of decreased HR. These results need to be replicated in a larger cohort before developing patterned stimulation using VNS to stabilize cardiac dysautonomia and prevent fatal arrhythmias.

Sphingosine 1-Phosphate: A Novel Target for Lung Disorders.

Sphingosine 1-phosphate (S1P) is involved in a wide range of cellular processes, which include proliferation, apoptosis, lymphocyte egress, endothelial barrier function, angiogenesis, and inflammation. S1P is produced by two isoenzymes, namely, sphingosine kinase 1 and 2 (SphK1 and 2) and once produced, S1P can act both in an autocrine and paracrine manner. S1P can be dephosphorylated back to sphingosine by two phosphatases (SGPP 1 and 2) or can be irreversibly cleaved by S1P lyase. S1P has a diverse range of functions, which is mediated in a receptor dependent, through G-protein coupled receptors (S1PR1-5) or receptor independent manner, through intracellular targets such as HDACs and TRAF2. The involvement of S1P signaling has been confirmed in various disease conditions including lung diseases. The SphK inhibitors and S1PR modulators are currently under clinical trials for different pathophysiological conditions. There is a significant effort in targeting various components of S1P signaling for several diseases. This review focuses on the ways in which S1P signaling can be therapeutically targeted in lung disorders.

Multiplexed single-mode wavelength-to-time mapping of multimode light.

When an optical pulse propagates along an optical fibre, different wavelengths travel at different group velocities. As a result, wavelength information is converted into arrival-time information, a process known as wavelength-to-time mapping. This phenomenon is most cleanly observed using a single-mode fibre transmission line, where spatial mode dispersion is not present, but the use of such fibres restricts possible applications. Here we demonstrate that photonic lanterns based on tapered single-mode multicore fibres provide an efficient way to couple multimode light to an array of single-photon avalanche detectors, each of which has its own time-to-digital converter for time-correlated single-photon counting. Exploiting this capability, we demonstrate the multiplexed single-mode wavelength-to-time mapping of multimode light using a multicore fibre photonic lantern with 121 single-mode cores, coupled to 121 detectors on a 32 × 32 detector array. This work paves the way to efficient multimode wavelength-to-time mapping systems with the spectral performance of single-mode systems.

Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor.

The gastrointestinal (GI) tract has a central role in nutritional homeostasis, as location for food ingestion, digestion and absorption, with the gut endocrine system responding to and regulating these events, as well as influencing appetite. One key GI hormone with the full spectrum of these activities is cholecystokinin (CCK), a peptide released from neuroendocrine I cells scattered through the proximal intestine in response to fat and protein, with effects to stimulate gall bladder contraction and pancreatic exocrine secretion, to regulate gastric emptying and intestinal transit, and to induce satiety. There has been interest in targeting the type 1 CCK receptor (CCK1R) for drug development to provide non-caloric satiation as an aid to dieting and weight loss; however, there have been concerns about CCK1R agonists related to side effects and potential trophic impact on the pancreas. A positive allosteric modulator (PAM) of CCK action at this receptor without intrinsic agonist activity could provide a safer and more effective approach to long-term administration. In addition, CCK1R stimulus-activity coupling has been shown to be negatively affected by excess membrane cholesterol, a condition described in the metabolic syndrome, thereby potentially interfering with an important servomechanism regulating appetite. A PAM targeting this receptor could also potentially correct the negative impact of cholesterol on CCK1R function. We will review the molecular basis for binding natural peptide agonist, binding and action of small molecules within the allosteric pocket, and the impact of cholesterol. Novel strategies for taking advantage of this receptor for the prevention and management of obesity will be reviewed.

The class B G-protein-coupled GLP-1 receptor: an important target for the treatment of type-2 diabetes mellitus.

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone secreted from L cells in the distal small intestine and proximal colon after a meal that acts as an incretin to augment the insulin response, while also inhibiting glucagon and slowing gastric emptying. These characteristics of GLP-1, as well as its ability to reduce islet beta cell apoptosis and expand beta cell mass and its cardioprotective and neuroprotective effects, provide a broad spectrum of actions potentially useful for the management of type-2 diabetes mellitus. GLP-1 also has the added advantage of having its incretin effects dependent on the level of serum glucose, only acting in the presence of hyperglycaemia, and thereby preventing hypoglycemic responses. Although natural GLP-1 has a very short half-life, limiting its therapeutic usefulness, a variety of analogues and formulations have been developed to provide extended actions and to limit side effects. However, all of these peptides require parenteral administration. Potentially orally active small-molecule agonists acting at the GLP-1 receptor are also being developed, but have not yet been approved for clinical use. Recent insights into the molecular nature of the class B G-protein-coupled GLP-1 receptor has provided insights into the modes of binding these types of ligands, as well as providing opportunities for rational enhancement. The advantages and disadvantages of each of these agents and their possible clinical utility will be explored.

Pregnancy outcomes with thyroxine replacement for subclinical hypothyroidism: Role of thyroid autoimmunity.

OBJECTIVE: To study pregnancy outcomes in relation to thyroid peroxidase antibody (TPOAb) status with optimum thyroxine replacement for subclinical hypothyroidism. MATERIALS AND METHODS: Ninety-eight women with subclinical hypothyroidism were followed up until the end of their pregnancy. TPO antibody status was performed for 59 women (positive 20, negative 39). Levothyroxine was supplemented to maintain TSH between 0.3-3 mIU/l in all patients, irrespective of TPOAb status. Pregnancy outcomes were noted as pregnancy-induced hypertension (PIH), antepartum or postpartum hemorrhage, preterm delivery, and spontaneous abortion. Outcomes were compared between 3 groups as per TPO antibody status (positive, negative, and undetermined), which were matched for age and gestational period. RESULTS: Thyroid autoimmunity was noted in 34% of women screened for TPO antibody. A total of 11 adverse pregnancy outcomes were recorded (4 spontaneous abortions, 4 preterm deliveries, 3 PIH) with no significant difference between the groups. CONCLUSION: Adverse pregnancy outcomes were not different in the 3 groups with adequate thyroxine replacement for pregnant women with subclinical hypothyroidism targeting TSH in euthyroid range, irrespective of thyroid autoimmunity status.

Stereo-isomerism controls surface reactivity: 1-chloropentane-pairs on Si(100)-2×1.

Chloropentane forms asymmetric ('A') and symmetric ('S') pairs on Si(100)-2×1, differing in the direction of curvature of one pentane tail. Surprisingly this renders the rate of thermal reaction of 'A' fifteen times greater than 'S' in chlorinating room-temperature silicon. Correspondingly, for electron-induced reaction the energy threshold for A is 1 eV less than for S.

Directed long-range molecular migration energized by surface reaction.

The recoil of adsorbates away (desorption) and towards (reaction) surfaces is well known. Here, we describe the long-range recoil of adsorbates in the plane of a surface, and accordingly the novel phenomenon of reactions occurring at a substantial distance from the originating event. Three thermal and three electron-induced surface reactions are shown by scanning tunnelling microscopy to propel their physisorbed ethylenic products across the rough surface of Si(100) over a distance of up to 200 Å before an attachment reaction. The recoil energy in the ethylenic products comes from thermal exoergicity or from electronic excitation of chemisorbed alkenes. We propose that the mechanism of migration is a rolling motion, because the recoiling molecule overcomes raised surface obstacles. Electronic excitation of propene causes directional recoil and often end-to-end inversion, suggesting cartwheeling. Ab initio calculations of the halogenation and electron-induced reactions support a model in which asymmetric forces between the molecule and the surface induce rotation and therefore migration.