Slow Onset Research Articles

Force mechanism analysis of composite microbial dust suppressants based on extracellular polymeric substances (EPS) mode components

As an important potential dust suppression method, the slow onset time is one of the key factors that restrict the effect of microbial dust suppressant. In the early stage, we have confirmed that extracellular polymeric substances (EPS) can improve the dust suppression effect by wetting coal dust and increasing Ca2+ nucleation sites. Therefore, in this study, chitosan (CTS) and bovine serum albumin (BSA) in different ratios (CTS: BSA = 1:1, 1:2, 2:1) as model molecules of EPS were combined with Bacillus subtilis to prepare efficient and fast microbial dust suppressants. Furthermore, the interaction forces were analyzed through molecular dynamics simulation. Results showed that adding CTS and BSA would improve the dust suppression effect, and the dust suppression effect was the best when the ratio of CTS: BSA was 1:2. In addition, the contact angle decreased as the BSA content increased. The Fourier transform infrared spectroscopy (FTIR) results showed that when the ratio of CTS to BSA was 1:2, the dust suppressants were easier to interact with coal dust by the key functional groups and form calcite type CaCO3. The molecular dynamics simulation results showed that the main interaction was Van der Waals force. In addition, the interaction force was strongest when CTS: BSA was 1:2, increasing by 137% compared with the microbial dust suppressants without CTS or BSA. This study provides theoretical support for the development of efficient and rapid microbial dust suppressants.

Attribution of environmental outcomes to climate change: Perceptions of coastal communities in the Caribbean

Attribution of environmental outcomes to climate change is a live debate in scholarly and policy circles. Non-scientific attribution by the lay public has value for enriching the discourse, engagements, and decisions on loss and damage, adaptation and mitigation, communication strategies, and the science-policy interface from local to international levels. There is a need for context-specific studies on perceived climate attribution by the lay public. Unlike the few previous studies that focused on attribution of extreme events to climate change by the lay public, the current paper assessed the key compositional and contextual factors that influence the attribution of environmental outcomes with slow onset to climate change. This study surveyed 441 households in eight small coastal communities in three Caribbean countries and applied a generalized linear regression model with a complementary log-log link to assess the relationship between compositional and contextual factors that influence perceived linkage between climate change and environmental outcome. At the bivariate level, the results showed that ethnicity, marital status, household head highest education, household income, and community of living were significant predictors of the likelihood of the perceived linkage between climate change and worsening environmental outcome. At the multivariate level, when all factors have been accounted for, we found that respondents with higher education were 160% more likely to indicate that climate change has adverse effects on environmental outcomes. Respondents with 10 or more years of experience in their present occupation were 73% more likely to suggest a linkage between climate change and worse environmental outcomes. Other strong predictors included income, ethnicity and community of residence. The perceived relationship between climate change and environmental outcomes differed systematically based on the compositional and contextual attributes of respondents. Several significant relationships at the bivariate level persisted at the multivariate level, indicating that the perceived linkages are robust and entrenched. It is concluded that there are heterogeneities in the perceived relationship between climate change and environmental outcomes based on the compositional and contextual factors of the households. Higher education and longer experience in the same occupation contribute significantly to climate attribution by the lay public.

9388 Unusual Case Of Ectopic Adrenocorticotropic Hormone Syndrome Secondary To Non-small Cell Lung Cancer

Abstract Disclosure: A. TakallooBakhtiari: None. G.L. Nunlee-Bland: None. V. Ganta: None. A. Zenebe: None. H. Abdalla: None. A. Elobeid: None. W.A. Odonkor: None. Introduction: Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition due to adrenocorticotropic hormone (ACTH) release from non-pituitary tumors. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The most common cause of EAS is lung cancer. Cushing syndrome (CS) due to EAS is an uncommon paraneoplastic phenomenon in non-small cell lung cancer. Clinical case: The patient is an 80-year-old man with a past medical history of hypertension, dementia, stroke, schizophrenia, and recently diagnosed lung adenocarcinoma. He presented with a few weeks history of dysuria and generalized fatigue. There was no family history for any endocrine disorders. He has a 40 pack-year history of tobacco use. He denied alcohol or illicit drug use. Upon initial evaluation, VS: BP 155/95 mmHg, HR 82 beats/min, Ht 77 inches, Wt 125 lb with a BMI 14.7 Kg/m2. He had no typical symptoms of CS. A physical exam showed a cachectic man with no other remarkable findings. Laboratory tests on admission showed severe hypokalemia of 1.8 mEq/L (3.5-5 mEq/L) with hypochloremic metabolic alkalosis. (bicarbonate 45 mEq/L (22-28 mEq/L) and chloride 79 mEq/L (96-106 mEq/L)). Patient was normoglycemic with HbA1c of 5.0%. Random morning cortisol was 55 μg/dL (13-24 μg/dL). Supine renin and aldosterone levels were 0.45 ng/ml/h (0.25-5.8 ng/ml/h) and 1.0 ng/dL (3-16 ng/dL), respectively, excluding hyperaldosteronism. Beside urinary tract infection, other biochemical workup revealed elevated 24-h urinary free cortisol level 5233 mcg/24h (4.0-50.0 mcg/24h) with creatinine 0.7 g/24h (0.5-2.15 g/24h). Failure to suppress cortisol with low dose dexamethasone suppression test (LDDST) was evident: morning cortisol >60.0 g/dL , with concurrent serum dexamethasone 299 ng/dL (180-550 ng/dL). Plasma ACTH level was elevated 327 pg/ml (6-50 pg/ml), favoring ACTH-dependent CS. A magnetic resonance imaging (MRI) of the sella and computed tomography (CT) of the abdomen did not show pituitary or adrenal masses. Therefore, a diagnosis of ectopic CS due to lung cancer was established. Pathology of the lung mass showed tumor cells were negative for synaptophysin, chromogranin, and CD52. The immunohistochemically findings support primary adenocarcinoma of the lung. Patient refused surgical or medical treatment and was discharged to a hospice facility. Conclusion: The clinical presentation of EAS ranges from the abrupt onset of the signs and symptoms of severe hypercortisolism, including hypertension, hypokalaemia, metabolic alkalosis as in our patient to the gradual and slow onset of the classical signs and symptoms of CS. Though EAS with adenocarcinoma of the lung is rare, it is important to consider it within the differential diagnosis of any adenocarcinoma of the lung presenting with the relevant symptoms. Presentation: 6/3/2024

Pediatric Rhegmatogenous Retinal Detachment and its Treatment

Pediatric rhegmatogenous retinal detachments have a different clinical presentation and different treatment algorithms than adult rhegmatogenous retinal detachments. The absence of posterior vitreus detachment and the predominance of retinal holes and dialysis in the etiology can be counted among these differences. Slow onset of visual loss and the inability of the pediatric age group to appreciate the symptoms leads to the development of variable amounts of proliferative vitreoretinopathy at clinical presentation. The presence of the crystalline lens and exaggerated wound healing response of the young eye changes the usual treatment approach of the adult detachments, and combination surgeries are frequently required. Scleral buckling surgery is the primary treatment option in the pediatric age group. It may be applied segmentally or circumferentially according to the level of the retinal breaks and the extent proliferative vitreoretinopathy present. Vitrectomy may be added according to the treatment response or the level of proliferative vitreoretinopathy present. Phakic lens status, abnormally posterior insertion of posterior vitreus base, and hyalocyte cellular remnants despite successful intraoperative posterior vitreus detachment are the obstacles that may be encountered in vitrectomy for pediatric retinal detachment. Pediatric rhegmatogenous retinal detachments require a higher number of surgeries per patient and have a lower final retinal attachment rate than adult cases. Examination and prophylactic treatment of the fellow eye must be carried out as the underlying retinal breaks and predisposing lesions are frequently bilateral with the exception of trauma in this age group.

Polysomnographically mediated cognitive improvements in individuals with insomnia symptoms following continuous theta-burst stimulation of the default mode network

IntroductionInsomnia is associated with mild cognitive impairment, although the mechanisms of this impairment are not well-understood. Timing of slow-wave and rapid eye movement sleep may help explain cognitive impairments common in insomnia. This investigation aimed to determine whether cognitive changes following continuous theta-burst stimulation (cTBS) are attributable to active stimulation, polysomnographic parameters of sleep, or both.MethodData presented here are part of a pilot clinical trial aiming to treat insomnia by targeting a node in the default mode network using an inhibitory 40-s (cTBS). A double-blind counterbalanced sham-controlled crossover design was conducted. Participants (N = 20) served as their own controls on two separate in-laboratory visits—one with active cTBS and the other with sham cTBS. Each visit included cognitive assessments before and after stimulation and following a night of sleep in the lab monitored with polysomnography.ResultsSlow wave sleep duration influenced working memory in the active cTBS condition, with shorter duration predicting improvements in working memory post sleep (B = −0.003, p = 0.095). Onset latency to rapid eye movement sleep predicted subsequent working memory, regardless of treatment condition (B = −0.001, p = 0.040). Results suggest that changes in attention and processing speed were primarily due to slow wave sleep onset (B = −0.001, p = 0.017) and marginally predicted by slow wave sleep duration (B = 0.002, p = 0.081) and sleep efficiency (B = 0.006, p = 0.090).ConclusionsFindings emphasize the important role that timing of slow-wave and rapid eye movement sleep have on information processing. Future work using larger sample sizes and more stimulation sessions is needed to determine optimal interactions between timing and duration of slow wave and rapid eye movement throughout the sleep period.Clinical trial registrationThis study is registered on ClinicalTrials.gov (NCT04953559). https://clinicaltrials.gov/study/NCT04953559?locStr=Arizona&country=United%20States&state=Arizona&cond=insomnia&intr=tms%20&rank=1

Exploring the relationship between climate change events and migration decisions: Evidence from a choice experiment in Bangladesh

Bangladesh is a low-lying deltaic nation with high vulnerability to climate-related hazards. Hatiya Island is located in Southern Bangladesh, and residents rely significantly on fishing and agriculture for their livelihoods. However, the island's primary production systems face a threat from intense and frequent sudden onset environmental hazards such as river erosion, cyclones, and flooding, as well as slow onset environmental hazards like saline intrusion, tidal inundation, and rising temperatures. Little is known about the effect sudden onset and slow onset hazards have on the migration patterns of Hatiya's residents. The aim of this study is to investigate the relationship between climatic events and the migration decisions of residents on Hatiya Island. To explore this link, we collected empirical data from 337 respondents on Hatiya Island using a choice experiment survey. The five attributes were used to construct migration scenarios, including climate events at Hatiya Island, the distance of migration, the migration type, the social network at the potential destination, and the difference in income between Hatiya Island and the potential destination. The findings from the mixed logit model indicated that climate events at Hatiya, migration distance, and income gap affected residents' migration decisions. Extreme slow onset change and extreme sudden onset change were less likely to induce migration compared to the moderate level of slow and sudden onset change. However, residents were more likely to migrate as the income difference between Hatiya and the prospective destination increased. Residents were willing to migrate at a 9.4 % increase in income for extreme sudden onset change, while residents required a 14.19 % increase in income to migrate in response to extreme slow onset change. As such, policies are needed to support migrants in receiving areas through improved social protection systems, to support migrant-sending households' transformative adaptation in origin areas, and to bolster community-driven adaptation initiatives in Hatiya. The findings from this study can contribute to the existing literature on the relationship between environmental hazards and mobility and inform policymakers on how to design policies that support vulnerable populations.

Comparing the Efficacy of 8.4% and 7.5% Buffered Lidocaine during Surgical Removal of Impacted Mandibular Third Molar- A Split Mouth Double Blinded Randomized Controlled Study.

Conventional injection technique with adrenaline during removal of impacted third molar of mandible had proportionally increased pain during administration with slow onset of action and shorter duration of anesthesia. The purpose of this study was to compare the effective nature of 8.4% and 7.5% buffered lidocaine hydrochloride during surgical removal of mandibular impacted third molar. This prospective crossover study included 50 patients requiring bilateral removal of impacted mandibular third molars. Group I included 50 impacted mandibular third molars that were administered with 8.4% buffered lidocaine hydrochloride and group II included 50 impacted mandibular third molars were administered with 7.5% buffered lidocaine hydrochloride. The outcome variables were pain on injection, time of onset of anesthesia, and duration of action of anesthesia. The above parameters were recorded by the investigator and statistically analyzed through Chi-square test using SPSS software. Patients in group I had mild pain (1.02) and patients in group II (5.74) had moderate pain with a statistical significance of p< 0.05 for group I respectively. The mean onset of action of anesthesia in group I was 0.08 seconds and 0.59 seconds in group II (p< 0.05). The duration of anesthesia was 342.51 minutes from group I and 122.06 minutes in group II (p< 0.05) respectively. Lidocaine hydrochloride buffered with 8.4 % sodium bicarbonate was found to be more effective in reduction of pain during injection, also had a faster onset of action and longer duration of the action of anesthesia when compared to 7.5% buffered lidocaine hydrochloride.

METHOXYFLURANE: A HISTORICAL REVIEW AND SAFETY ANALYSIS OF ITS USE AS AN ANALGESIC IN EMERGENCY AND OUTPATIENT PROCEDURES

OMethoxyflurane, introduced as an anesthetic agent in the 1960s, quickly gained popularity due to its potent properties. However, its use as an anesthetic was discontinued due to significant side effects, particularly nephrotoxicity, manifested as acute renal failure with high diuresis. By the mid-1970s, methoxyflurane was withdrawn from the anesthetic market in North America and gradually worldwide. It was later discovered that low-dose methoxyflurane had powerful analgesic properties, allowing its use for short-term pain relief in traumatic injuries and during ambulatory procedures. Australian emergency services began using portable methoxyflurane inhalers for emergency care. Clinical trials confirmed the effectiveness of this agent, with no significant side effects such as renal or hepatic toxicity reported. The physicochemical properties of methoxyflurane, particularly its high lipid solubility and low vapor pressure, provide a slow onset of sedation, limiting its sedative effects when used short-term. Clinical studies have confirmed the safety and efficacy of methoxyflurane in conducting ambulatory procedures such as colonoscopy and burn wound dressing changes. Methoxyflurane reduces anxiety and pain, allowing patients to return to normal activities more quickly. Thus, methoxyflurane, used as a low-dose inhaled analgesic, can be an effective and safe pain relief option during ambulatory medical and surgical procedures, particularly in patients at high risk of complications from traditional sedation methods. Further research, including large randomized controlled trials, may provide additional evidence to support the potential benefits of methoxyflurane.

Neuroprotection of low dose carbon monoxide in Parkinson’s disease models commensurate with the reduced risk of Parkinson’s among smokers

Paradoxically, cigarette smoking is associated with a reduced risk of Parkinson’s Disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on α-synuclein (αSyn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces αSyn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting αSyn degradation, thereby conferring neuroprotection. Consistent with the neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without αSyn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO-modulated pathways to slow symptom onset and limit pathology in PD patients.

A Buffered Local Anesthetic Without Epinephrine: Development, Characterization, and In Vivo Efficacy and Toxicity Analysis.

Lidocaine hydrochloride (HCl) 2% with 1:100,000 epinephrine (LW/E) is widely used to prevent pain during dental procedures and has been associated with injection sting, jittering effects, slow onset, and a bitter aftertaste. Since LW/E's introduction in 1948, no significant modifications have been proposed. This study aims to design and characterize an improved dental lidocaine HCl injectable formulation without epinephrine (LW/O/E) via buffers, sweeteners, and amino acids. LW/O/E injections were prepared with pH and osmolality values of 6.5-7.0 and 590-610 mOsm/kg. Using the electronic tongue (ETongue), the LW/O/E injectable formulations were characterized for viscosity, injectability, and taste analysis. The results were compared with the LW/E control. In vivo efficacy and anesthetic duration of the samples were measured through radiant heat tail-flick latency (RHTFL) and hot plate (HP) tests and local toxicity was assessed after a single intra-oral injection in Sprague Dawley rats (SDR). The viscosity and injectability values of the LW/O/E samples were found to be comparable to the LW/E injection. ETongue taste analysis showed an improvement in bitterness reduction of the LW/O/E samples compared to the LW/E formulation. Toxicity studies of samples in SDR showed minor and transient signs of erythema/eschar and edema. Anesthetic duration via RHTFL and HP paw withdrawal latency time in SDR were found to be comparable for the LW/O/E Sample 3A and the LW/E injection (p < 0.05). In conclusion, the buffered, higher osmolality and reduced bitterness developed LW/O/E formulation (Sample 3A) could be considered a promising alternative to the LW/E formulation for dental use.

Discovery of Multi-functional Lead Compounds Originating from Traditional Chinese Medicine for Developing Anti-depressive Agents via Virtual Screening

Background: The increasing prevalence of depression has become a global health issue. Currently approved anti-depressive including 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), triple reuptake inhibitors (TRIs) and glutamate N-methyl-D-aspartate (NMDA) receptor antagonists have limited effects because of their insufficient efficacy and/or slow onset of action. Developing multifunctional antidepressants that can modulate 5-HT, DA, NE, and NMDA simultaneously can potentially overcome the current drug defects. Objective: This study aimed to explore leads for the development of multi-functional anti-depressive agents that simultaneous triple reuptake inhibitory and NMDA-GluN2B receptor antagonistic activities. Methods: Potential leads were screened virtually from the TCMSP database based on the 3DPharmacophore model of TRIs followed by the molecular docking into NMDA-GluN2B receptor, BBB score, and the in silico toxicity evaluation. The biological activities of discovered leads on 5-HT, NE, and DA reuptake and their effect on the NMDA-GluN2B receptor were evaluated via radio-labeled neurotransmitters and competition radio-ligand binding experiment with [3H] ifenprodil, respectively. Lastly, the antidepressant effect of these potential leads was determined in vivo through the forced swim test in mice. Results: Two compounds were attained as potential leads after the aforementioned experiments. Further in vitro biological evaluation identified Hit-2 as a promising lead that exerted favorable triple 5- HT/DA/NE reuptake inhibitory activity (66.98% inhibition rate at 10 μM against hNET, 73.01% inhibition rate at 1 μM against hDAT and 86.27% inhibition rate at 1 μM against hSERT), as well as potent NMDA-GluN2B receptor antagonistic activity (Ki=115.73 ± 3.54 nM). The antidepressant activity of Hit- 2 was confirmed through in vivo experiments Conclusion: Hit-2 not only simultaneously inhibited the reuptake of 5-HT, DA, and NE, and acted as an NMDA-GluN2B receptor antagonist in vitro but also showed in vivo antidepressant activity. These findings may serve as a structural basis for the further development of multi-functional anti-depressive agents.

Nanodelivery Optimization of IDO1 Inhibitors in Tumor Immunotherapy: Challenges and Strategies.

Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.

Terapi &lt;i&gt;Montelukast &lt;/i&gt;pada Asma

Asthma is a chronic inflammatory respiratory condition caused by various inflammatory mediators, including those from the arachidonic acid pathway, which serves as a precursor for leukotrienes and prostaglandins. Leukotriene receptor antagonists (LTRAs) have been approved since 1998 as a treatment for asthma. Montelukast is one of the LTRAs that is useful for asthma control, including cases that accompanied by allergic rhinitis. A daily dose of 5-10 mg is recommended for persistent asthma as the preferred controller. LTRAs are not recommended for acute asthma exacerbation due to their relatively slow onset, but they are beneficial in preventing exacerbations. They are also indicated for exercise-induced asthma (EIA), and can be taken 2 hours prior to exercise. Montelukast can be administered as monotherapy or added to LABA-ICS therapy. It is suitable for adults, children, and infants over 1 year of age, preferably taken at night to prevent symptoms in the early morning. Possible side effects include respiratory tract infections, abdominal pain, diarrhea, and neuropsychiatric disorders. Montelukast is considered safe for use during pregnancy and breastfeeding. Physicians should provide comprehensive education for patients regarding medication compliance and the potential risks of side effects. Regular daily use of montelukast is beneficial in preventing acute exacerbations in asthma patients.

Phagocytosis of aggrecan-positive perineuronal nets surrounding motor neurons by reactive microglia expressing MMP-9 in TDP-43Q331K ALS model mice

Perineuronal nets (PNNs) are extracellular matrix structures that surround excitable neurons and their proximal dendrites. PNNs play an important role in neuroprotection against oxidative stress. Oxidative stress within motor neurons can act as a trigger for neuronal death, and this has been implicated in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We therefore characterised PNNs around alpha motor neurons and the possible contributing cellular factors in the mutant TDP-43Q331K transgenic mouse, a slow onset ALS mouse model. PNNs around alpha motor neurons showed significant loss at mid-stage disease in TDP-43Q331K mice compared to wild type strain control mice. PNN loss coincided with an increased expression of matrix metallopeptidase-9 (MMP-9), an endopeptidase known to cleave PNNs, within the ventral horn. During mid-stage disease, increased numbers of microglia and astrocytes expressing MMP-9 were present in the ventral horn of TDP-43Q331K mice. In addition, TDP-43Q331K mice showed increased levels of aggrecan, a PNN component, in the ventral horn by microglia and astrocytes during this period. Elevated aggrecan levels within glia were accompanied by an increase in fractalkine expression, a chemotaxic protein responsible for the recruitment of microglia, in alpha motor neurons of onset and mid-stage TDP-43Q331K mice. Following PNN loss, alpha motor neurons in mid-stage TDP-43Q331K mice showed increased 3-nitrotyrosine expression, an indicator of protein oxidation. Together, our observations along with previous PNN research provide suggests a possible model whereby microglia and astrocytes expressing MMP-9 degrade PNNs surrounding alpha motor neurons in the TDP-43Q331K mouse. This loss of nets may expose alpha-motor neurons to oxidative damage leading to degeneration of the alpha motor neurons in the TDP-43Q331K ALS mouse model.

A systematic approach to the management of menses prophylaxis and suppression in pre-menopausal hematologic cancer patients.

Hematologic malignancies in women of reproductive age carry significant additional morbidity due to menstrual bleeding in conjunction with disease and treatment-associated cytopenias. Several agents for menses prophylaxis and suppression exist, but there is a paucity of data comparing these therapies, particularly in the cancer setting. A thorough literature review and evaluation of available data was conducted via PubMed search and combined with clinical expertise. The goal of prophylaxis therapy is to induce amenorrhea until it is considered safe to resume menstrual cycles. GnRH agonists remain the management of choice in achieving menses control and amenorrhea. Suppression is more likely achieved when the therapy is initiated in the late luteal phase or with the concomitant use of oral contraceptives. The effective use of oral contraceptives is achievable in appropriately selected patients. Although attractive as prophylactic agents, GnRH agonists have a slow onset of amenorrhea and can be associated with an initial increase in bleeding, thus are of limited value in immediate menorrhagia management. We recommend prioritizing estrogen therapy given its documented efficacy, and adding tranexamic acid as a secondary agent for severe or refractory bleeding. Thus far in the literature, this is the most comprehensive proposed pathway for the prevention and suppression of menorrhagia in hematologic cancer patients. Our protocol provides a step-wise approach for the management of menses prophylaxis and suppression to provide standardization amongst clinicians and adaptations for patient-specific needs.

Comparison of Fentanyl With Midazolam As Adjuvants to Levobupivacaine in Spinal Anesthesia for Cesarean Sections: A Randomized Controlled Trial.

Background and objectives Spinal anesthesia stands as a cornerstone for patients undergoing lower segment cesarean section (LSCS), offering advantages like faster onset and high block density. Levobupivacaine, known for its high potency and long-acting nature, has a slower onset. The safety of intrathecal fentanyl or midazolam is evaluated as an adjuvant to levobupivacaine in parturients. This study aims to compare the duration of postoperative analgesia provided by fentanyl or midazolam added to 0.5% hyperbaric levobupivacaine in elective cesarean sections. Secondary objectives include evaluating the onset and duration of sensory and motor blockade and the incidence of nausea and vomiting. Identifying the more effective adjuvant will help optimize spinal anesthesia protocols, improve postoperative outcomes, and enhance patient comfort and recovery. Methods This study was conducted at SRM Medical College Hospital and Research Centre, Chennai, India, over six months (May 1, 2023, to October 1, 2023). A total of 90 patients undergoing elective LSCS received spinal anesthesia in a prospective randomized double-blinded controlled trial. Patients were allocated to three groups: Group A received levobupivacaine with fentanyl, Group B received levobupivacaine with midazolam, and Group C received levobupivacaine with normal saline. Block characteristics, postoperative analgesia, hemodynamic stability, and complications were assessed. Assessments were conducted at specified time points: intraoperatively, every five minutes for the first 30 minutes, every 10 minutes for the next hour, every two hours for six hours, and every four hours up to 24 hours postoperatively. Statistical analysis utilized one-way analysis of variance (ANOVA). Results Group B (levobupivacaine with midazolam) exhibited a shorter time to sensory block onset (88 seconds) compared to Groups A and C (both 145 seconds) (p < 0.001). Group A (levobupivacaine with fentanyl) showed a shorter time to maximum motor block (p = 0.045) than Groups B and C. The sensory block duration was significantly longer in Group A (127.5 minutes) compared to Group B (60 minutes) and Group C (69 minutes) (p < 0.001). Motor block duration was also prolonged in Group A (251 minutes) compared to Group B (147 minutes) and Group C (177 minutes) (p = 0.045). The first analgesic requirement was delayed in Group A (248 minutes), whereas Groups B (115 minutes) and C (90 minutes) (p < 0.001) required more frequent analgesia. Group A experienced a higher incidence of postoperative nausea and vomiting. Conclusion Midazolam accelerated sensory block onset, while fentanyl prolonged anesthesia duration without significantly affecting motor block. Fentanyl delayed the first analgesic requirement, whereas midazolam reduced postoperative nausea, vomiting, and shivering.

Constraining Displacement Magnitude on Crustal‐Scale Extensional Faults Using Thermochronology Combined With Flexural‐Kinematic and Thermal‐Kinematic Modeling: An Example From the Teton Fault, Wyoming, USA

AbstractConstraining the geometry and displacement of crustal‐scale normal faults has historically been challenging, owing to difficulties with geophysical imaging and inability to identify precise cut‐offs at depth. Using a modified workflow previously applied to contractional systems, flexural‐kinematic (Move) and thermal‐kinematic (Pecube) models are integrated with apatite (U‐Th)/He (AHe) and apatite fission track (AFT) data from Teton footwall transects to constrain total Teton fault displacement (Dmax). Models with slip onset at ∼10 Ma and flexure parameters that best match the observed Teton flexural profile require Dmax &gt; 8 km to produce young (&lt;10 Ma) AHe ages observed at low elevation footwall positions in the Tetons. For the same slip onset, models with Dmax of 11–13 km provide the best match to observed AHe data, but displacements ≥16 km are required to produce observed AFT ages (13.6–12.0 Ma) at low elevations. A more complex model with slow slip onset at ∼25 Ma followed by faster slip at ∼10 Ma yields a good match between modeled and observed AHe ages at a Dmax of 13–15 km. However, this model predicts low elevation AFT ages 6–8 Ma older than observed ages, even at Dmax values of 16–17 km. Based on this analysis and integration with previous studies, we propose a unified evolution wherein the Teton fault likely experienced 11–13 km of Miocene‐recent displacement, with AFT data likely indicating a pre‐to early Miocene cooling history. Importantly, this study highlights the utility of using integrated flexural‐ and thermal‐kinematic models to resolve displacement histories in extensional systems.

Efficacy and safety of perioperative application of esketamine on postoperative depression: a meta-analysis of randomized controlled studies.

Postoperative depression has a profound impact on patients' postoperative rehabilitation and overall quality of life. Preventing postoperative depression is of significant value because conventional antidepressants have a slow onset of action. Esketamine showed prompt and sustained antidepressant efficacy. Nevertheless, the safety and effectiveness of perioperative esketamine in preventing postoperative depression are still unknown. The purpose of this meta-analysis was to assess the safety and effectiveness of perioperative intravenous esketamine in relation to its ability to prevent postoperative depression. Randomized controlled trials were searched in the following databases: Web of Science, Cochrane Central Registry of Controlled Trials, PubMed, and Embase. The primary outcome assessed is the postoperative depression scores. Postoperative pain ratings and adverse effects constituted secondary outcomes. Subgroup analyses were carried out on the basis of multiple variables, including the absence or presence of preoperative depression, the mode of esketamine administration, the dosage of esketamine, and the type of anesthesia. A total of 16 studies encompassed 1161 patients who received esketamine intervention, whereas 1106 patients served as controls. Esketamine was efficacious in reducing postoperative depression scores when administered perioperatively, and the esketamine group maintained a lower postoperative depression score than the control group more than four weeks after surgery. Esketamine effectively alleviated postoperative pain scores without increasing the occurrence of postoperative nausea and vomiting, dizziness, drowsiness, nightmares, and dissociation. The administration of esketamine during the perioperative has the potential to decrease postoperative depression and pain scores without increasing the incidence of adverse effects.

A comparative study of intrathecal isobaric ropivacaine and hyperbaric bupivacaine for elective lower segment caesarean section

Background: The study was to compare intrathecal isobaric ropivacaine and hyperbaric bupivacaine in terms of onset of sensory block, maximum height of sensory block, total sensory duration, onset of motor block, degree of motor block and duration of motor block, quality of anesthesia. Methods: The 100 cases of ASA II undergoing elective lower segment caesarean section were taken for the study and divided into two groups. Group B patients received 2 ml of hyperbaric bupivacaine intrathecally. Group R patients received 2ml of isobaric ropivacaine intrathecally. Patients were evaluated for onset and duration of sensory block, onset and duration of motor block, maximum height of sensory block, quality of anaesthesia, time to request for analgesia, hemodynamic parameters and side effects if any were studied. Results: There were no significant differences between the two groups in mean time to onset of sensory block. Maximum sensory height attained in group B ranged between T4 and T6, where as in group R, it ranged between T2 and T6 which was clinically and statistically highly significant (p&lt;0.001). Total duration of sensory block in group B and in group R, which is not significant (p=0.068). Mean time onset of motor block was 4min in group B and 8 min in group R, (p&lt;0.001). Duration of motor block was 155.20±14.95 min in group B and 94.10±8.31 min group R, which is clinically and statistically significant (p&lt;0.001). Conclusions: Ropivacaine 15 mg (2 ml of 0.75% isobaric ropivacaine) provides comparable quality of sensory block but has slower onset and significantly shorter duration of motor block compared to bupivacaine.

Feasibility of anomalous event detection based on Mobile Spatial Statistics: A study of six cases in Japan

One of the primary goals of disaster risk management is to minimize the loss of life in the event of a disaster. To reduce the number of victims in disasters is important to know the amount of exposed population to a hazard. Similarly, population distribution in real-time is required to estimate post-disaster needs and resources for disaster relief. In this study, we explore the use of Mobile Spatial Statistics (MSS) as the basis to acquire offline and online population data and detect anomalies that may relate to a disaster. For instance, mobile spatial data could identify sudden changes in the number of people indicating an anomalous event or change in population dynamics. Here we use the Matrix Profile (MP) method in time-series analysis to test the feasibility of detecting anomalies in the MSS data. We selected mass gatherings and disaster events with rapid and slow onset and small and large scales. We discuss the applicability of this method for real-time anomaly detection of spatial population distribution within the context of disaster risk management. Our results show that the applicability of the MP method in anomaly detection is sensitive to the size of the areas used during monitoring and analysis, the subsequence length and the threshold applied.