Aerial additive manufacturing with multiple autonomous robots.

Additive manufacturing methods1-4 using static and mobile robots are being developed for both on-site construction5-8 and off-site prefabrication9,10. Here we introduce a method of additive manufacturing, referred to as aerial additive manufacturing (Aerial-AM), that utilizes a team of aerial robots inspired by natural builders11 such as wasps who use collective building methods12,13. We present a scalable multi-robot three-dimensional (3D) printing and path-planning framework that enables robot tasks and population size to be adapted to variations in print geometry throughout a building mission. The multi-robot manufacturing framework allows for autonomous three-dimensional printing under human supervision, real-time assessment of printed geometry and robot behavioural adaptation. To validate autonomous Aerial-AM based on the framework, we develop BuilDrones for depositing materials during flight and ScanDrones for measuring the print quality, and integrate a generic real-time model-predictive-control scheme with the Aerial-AM robots. In addition, we integrate a dynamically self-aligning delta manipulator with the BuilDrone to further improve the manufacturing accuracy to five millimetres for printing geometry with precise trajectory requirements, and develop four cementitious-polymeric composite mixtures suitable for continuous material deposition. We demonstrate proof-of-concept prints including a cylinder 2.05 metres high consisting of 72 layers of a rapid-curing insulation foam material and a cylinder 0.18 metres high consisting of 28 layers of structural pseudoplastic cementitious material, a light-trail virtual print of a dome-like geometry, and multi-robot simulations. Aerial-AM allows manufacturing in-flight and offers future possibilities for building in unbounded, at-height or hard-to-access locations.

Frequency and predictors of concurrent complications in multi-suture release for syndromic craniosynostosis.

PURPOSE: Understanding the complication profile of craniosynostosis surgery is important, yet little is known about complication co-occurrence in syndromic children after multi-suture craniosynostosis surgery. We examined concurrent perioperative complications and predictive factors in this population. METHODS: In this retrospective cohort study, children with syndromic diagnoses and multi-suture involvement who underwent craniosynostosis surgery in 2012-2020 were identified from the National Surgical Quality Improvement Program-Pediatric database. The primary outcome was concurrent complications; factors associated with concurrent complications were identified. Correlations between complications and patient outcomes were assessed. RESULTS: Among 5,848 children identified, 161 children (2.75%) had concurrent complications: 129 (2.21%) experienced two complications and 32 (0.55%) experienced ≥ 3. The most frequent complication was bleeding/transfusion (69.53%). The most common concurrent complications were transfusion/superficial infection (27.95%) and transfusion/deep incisional infection (13.04%) or transfusion/sepsis (13.04%). Two cardiac factors (major cardiac risk factors (odds ratio (OR) 3.50 [1.92-6.38]) and previous cardiac surgery (OR 4.87 [2.36-10.04])), two pulmonary factors (preoperative ventilator dependence (OR 3.27 [1.16-9.21]) and structural pulmonary/airway abnormalities (OR 2.89 [2.05-4.08])), and preoperative nutritional support (OR 4.05 [2.34-7.01]) were independently associated with concurrent complications. Children who received blood transfusion had higher odds of deep surgical site infection (OR 4.62 [1.08-19.73]; p = 0.04). CONCLUSIONS: Our results indicate that several cardiac and pulmonary risk factors, along with preoperative nutritional support, were independently associated with concurrent complications but procedural factors were not. This information can help inform presurgical counseling and preoperative risk stratification in this population.

Disparities in indications and outcomes reporting for pediatric tethered cord surgery: The need for a standardized outcome assessment tool.

PURPOSE: Tethered cord syndrome (TCS) is characterized by abnormal attachment of the spinal cord neural elements to surrounding tissues. The most common symptoms include pain, motor or sensory dysfunction, and urologic deficits. Although TCS is common in children, there is a significant heterogeneity in outcomes reporting. We systematically reviewed surgical indications and postoperative outcomes to assess the need for a grading/classification system. METHODS: PubMed and EMBASE searches identified pediatric TCS literature published between 1950 and 2023. Studies reporting surgical interventions, ≥ 6-month follow-up, and ≥ 5 patients were included. RESULTS: Fifty-five studies representing 3798 patients were included. The most commonly reported non-urologic symptoms were nonspecific lower-extremity motor disturbances (36.4% of studies), lower-extremity/back pain (32.7%), nonspecific lower-extremity sensory disturbances (29.1%), gait abnormalities (29.1%), and nonspecific bowel dysfunction/fecal incontinence (25.5%). Urologic symptoms were most commonly reported as nonspecific complaints (40.0%). After detethering surgery, retethering was the most widely reported non-urologic outcome (40.0%), followed by other nonspecific findings: motor deficits (32.7%), lower-extremity/back/perianal pain (18.2%), gait/ambulation function (18.2%), sensory deficits (12.7%), and bowel deficits/fecal incontinence (12.7%). Commonly reported urologic outcomes included nonspecific bladder/urinary deficits (27.3%), bladder capacity (20.0%), bladder compliance (18.2%), urinary incontinence/enuresis/neurogenic bladder (18.2%), and nonspecific urodynamics/urodynamics score change (16.4%). CONCLUSION: TCS surgical literature is highly variable regarding surgical indications and reporting of postsurgical outcomes. The lack of common data elements and consistent quantitative measures inhibits higher-level analysis. The development and validation of a standardized outcomes measurement tool-ideally encompassing both patient-reported outcome and objective measures-would significantly benefit future TCS research and surgical management.

Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review.

INTRODUCTION: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes. METHODS: We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected. RESULTS: Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0-2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively. CONCLUSIONS: Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.

Current profile of phenotypic pyrethroid resistance in Rhipicephalus microplus (Acari: Ixodidae) populations sampled from Marathwada region of Maharashtra state, India.

This study examined the pattern of resistance to widely applied synthetic pyrethroids, i.e., cypermethrin and deltamethrin, against larvae of Rhipicephalus microplus ticks sampled from Marathwada region in Maharashtra, India. The study also examined the role of α- and ß-esterases and glutathione-S-transferase (GST) in resistance development. All eight R. microplus isolates tested were resistant to deltamethrin (RL IV), having RR50 values from 6.88 to 131.26. LPT analysis exhibited the resistance level II deltamethrin resistance in Beed and Hingoli, III in Dharashiv, and IV in Sambhajinagar, Parbhani, Latur, Jalna, and Nanded isolates. The LIT analysis showed that Dharashiv field isolates had the lowest LC50 value of 229.09 ppm against cypermethrin, while Sambhajinagar field isolates had the highest at 489.78 ppm. The RR50 ranged from 1145.45 to 2448.9. Seven isolates were level I resistant to cypermethrin while the Jalna isolate was level II resistant. In larvae treated with deltamethrin and cypermethrin, the activity of α- and ß-esterase enzymes increased significantly compared to control groups. The enzyme ratios in treated larvae ranged from 0.7533 to 1.7023 for α-esterase and 0.7434 to 3.2054 for ß-esterase. The Hingoli isolate treated with cypermethrin exhibited the highest α-esterase activity (903.261), whereas Sambhajinagar isolate had the highest GST enzyme ratio (2.8224) after deltamethrin exposure. When exposed to cypermethrin, the Hingoli isolate showed the highest GST enzyme ratio, 2.0832. The present study provides the current resistance status in tick populations from Marathwada region indicating deltamethrin and cypermethrin to be ineffective for tick control. The results also suggest that SP compounds should be regulated in this region and alternative control strategies should be introduced.

Anticancer perspectives of monocarbonyl analogs of curcumin: A decade (2014-2024) review.

Monocarbonyl analogs of curcumin (MACs) represent structurally modified versions of curcumin. The existing literature indicates that MACs exhibit enhanced anticancer properties compared with curcumin. Numerous research articles in recent years have emphasized the significance of MACs as effective anticancer agents. This review focuses on the latest advances in the anticancer potential of MACs, from 2014 to 2024, including discussions on their mechanism of action, structure-activity relationship (SAR), and in silico molecular docking studies.

Thermodynamic Stability Theories of Irreversible Processes and the Fourth Law of Thermodynamics.

Three approaches for determining the thermodynamic stability of irreversible processes are described in generalized formulations. The simplest is the Gibbs-Duhem theory, specialized to irreversible trajectories, which uses the concept of virtual displacement in the reverse direction. Its only drawback is that even a trajectory leading to an explosion is identified as a thermodynamically stable motion. In the second approach, we use a thermodynamic Lyapunov function and its time rate from the Lyapunov thermodynamic stability theory (LTS, previously known as CTTSIP). In doing so, we demonstrate that the second differential of entropy, a frequently used Lyapunov function, is useful only for investigating the stability of equilibrium states. Nonequilibrium steady states do not qualify. Without using explicit perturbation coordinates, we further identify asymptotic thermodynamic stability and thermodynamic stability under constantly acting disturbances of unperturbed trajectories as well as of nonequilibrium steady states. The third approach is also based on the Lyapunov function from LTS, but here we additionally use the rates of perturbation coordinates, based on the Gibbs relations and without using their explicit expressions, to identify not only asymptotic thermodynamic stability but also thermodynamic stability under constantly acting disturbances. Only those trajectories leading to an infinite rate of entropy production (unstable states) are excluded from this conclusion. Finally, we use these findings to formulate the Fourth Law of thermodynamics based on the thermodynamic stability. It is a comprehensive statement covering all nonequilibrium trajectories, close to as well as far from equilibrium. Unlike previous suggested "fourth laws", this one meets the same level of generality that is associated with the original zeroth to third laws. The above is illustrated using the Schlögl reaction with its multiple steady states in certain regions of operation.

Coumarin-4-yl-1,2,3-triazol-4-yl-methyl-thiazolidine-2,4-diones: Synthesis, glucose uptake activity and cytotoxic evaluation.

Thiazolidinedione (TZD) based medications have demonstrated to enhance the insulin sensitivity control, hyperglycemia, and lipid metabolism in patients with type 2 diabetes. Hence, in this study, a new series of novel coumarin-4-yl-1,2,3-triazol-4-yl-methyl-thiazolidine-2,4-diones (TZD1-TZD18) were synthesized via copper (I)-catalyzed azide-alkyne cycloaddition "Click Chemistry". The synthesized compounds were evaluated for their glucose uptake assay and in vitro cytotoxicity against HEK-293 (human embryonic kidney) cells which were compared with the standard drug Pioglitazone. Further, molecular docking analysis of these compounds was carried out to explain the in vitro results with PPARγ (PDB ID: 3CS8) and to better understand the bonding interactions with the target protein. The outcomes of in vitro assessment, molecular docking, and pharmacokinetics of the title compounds were revealed to be highly correlated. Interestingly, the compounds TZD4, TZD10, TZD14 and TZD16 were most efficient in lowering the blood glucose level compared with standard drug.

Prefrontal cortex output circuits guide reward seeking through divergent cue encoding.

The prefrontal cortex is a critical neuroanatomical hub for controlling motivated behaviours across mammalian species. In addition to intra-cortical connectivity, prefrontal projection neurons innervate subcortical structures that contribute to reward-seeking behaviours, such as the ventral striatum and midline thalamus. While connectivity among these structures contributes to appetitive behaviours, how projection-specific prefrontal neurons encode reward-relevant information to guide reward seeking is unknown. Here we use in vivo two-photon calcium imaging to monitor the activity of dorsomedial prefrontal neurons in mice during an appetitive Pavlovian conditioning task. At the population level, these neurons display diverse activity patterns during the presentation of reward-predictive cues. However, recordings from prefrontal neurons with resolved projection targets reveal that individual corticostriatal neurons show response tuning to reward-predictive cues, such that excitatory cue responses are amplified across learning. By contrast, corticothalamic neurons gradually develop new, primarily inhibitory responses to reward-predictive cues across learning. Furthermore, bidirectional optogenetic manipulation of these neurons reveals that stimulation of corticostriatal neurons promotes conditioned reward-seeking behaviour after learning, while activity in corticothalamic neurons suppresses both the acquisition and expression of conditioned reward seeking. These data show how prefrontal circuitry can dynamically control reward-seeking behaviour through the opposing activities of projection-specific cell populations.

An Initial Experience of Completion Hemispherotomy via Magnetic Resonance-Guided Laser Interstitial Therapy.

INTRODUCTION: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy. METHODS: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively. RESULTS: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8-12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342-1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2-3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246-475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0-5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384-918). No MRgLITT-related complications occurred. Delayed retreatment (>1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy. CONCLUSION: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted.

Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections.

OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST. METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated. RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications. CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.

The Fate of the Cervical Collar: An Observational Pilot Study Investigating Follow-up Care After Emergency Department Discharge in Children With Mild Traumatic Neck Injuries.

OBJECTIVES: After evaluation and treatment of minor traumatic cervical spine injury (CSI), many children are discharged home in a rigid cervical orthosis (RCO). This study investigated their adherence to RCO treatment recommendations. The feasibility of telehealth cervical spine clearance was also explored. METHODS: This was a prospective observational study of children 3 to 18 years old with mild CSI evaluated at a level I pediatric trauma center from December 1, 2019, through July 31, 2021. Before emergency department discharge, patients received RCO use instructions and recommendation for follow-up with in-person neurosurgery clinic visit, neurosurgery telehealth visit, or in-person primary care provider visit. The family was responsible for arranging follow-up. Primary outcomes included compliance with follow-up and collar use. RESULTS: Ninety-eight children (mean age, 11.3 ± 4.1 years) were included. Overall, follow-up contact was available for 51 patients (52%). At 1-week follow-up with 36 children, 64% were collar compliant, 13 had no pain (38% remained in RCO), 14 had mild pain without limitations, 8 had pain with some limitations, and 1 had significant pain. At 2-week follow-up with 31 children, 9 (29%) were collar compliant, 23 had no pain, 7 had mild pain without limitations, and 1 with significant persistent pain was found to have an odontoid fracture requiring C1-2 fusion. Patients/families often discontinued the use of the collar without follow-up (47%). Approximately half utilized a recommended clinical follow-up option for clearance, most often in neurosurgery clinic or using a neurosurgery telehealth visit. The mean time to follow-up was 11.34 ± 4.9 days (range, 3-25 days), and mean collar compliance lasted 9.8 ± 5.7 days (range, 1-25 days). No child experienced any short-term complications related to RCO use. CONCLUSIONS: In this pilot study, a substantial portion of children with mild CSIs discharged from the emergency department with an RCO did not adhere to compliance or follow-up recommendations. Persistent pain requires further evaluation.

Expression and Characterization of Intein-Cyclized Trimer of Staphylococcus aureus Protein A Domain Z.

Staphylococcus aureus protein A (SpA) is an IgG Fc-binding virulence factor that is widely used in antibody purification and as a scaffold to develop affinity molecules. A cyclized SpA Z domain could offer exopeptidase resistance, reduced chromatographic ligand leaching after single-site endopeptidase cleavage, and enhanced IgG binding properties by preorganization, potentially reducing conformational entropy loss upon binding. In this work, a Z domain trimer (Z3) was cyclized using protein intein splicing. Interactions of cyclic and linear Z3 with human IgG1 were characterized by differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC). DSF showed a 5 ℃ increase in IgG1 melting temperature when bound by each Z3 variant. SPR showed the dissociation constants of linear and cyclized Z3 with IgG1 to be 2.9 nM and 3.3 nM, respectively. ITC gave association enthalpies for linear and cyclic Z3 with IgG1 of -33.0 kcal/mol and -32.7 kcal/mol, and -T∆S of association 21.2 kcal/mol and 21.6 kcal/mol, respectively. The compact cyclic Z3 protein contains 2 functional binding sites and exhibits carboxypeptidase Y-resistance. The results suggest cyclization as a potential approach toward more stable SpA-based affinity ligands, and this analysis may advance our understanding of protein engineering for ligand and drug development.

How do children fare compared with adults? Comparing relative outcomes after thrombectomy for acute ischemic stroke due to large-vessel occlusion.

OBJECTIVE: Safety and efficacy data for endovascular thrombectomy for acute ischemic stroke secondary to large-vessel occlusion in children are lacking compared with those for adults. We undertook an updated systematic review and meta-analysis of endovascular thrombectomy in children and compared their outcomes with adult data. METHODS: We searched PubMed, Medline, and EMBASE databases to identify prospective and retrospective studies describing patients <18 years treated with endovascular thrombectomy for acute ischemic stroke due to large-vessel occlusion. RESULTS: Eight pediatric studies were included (n = 192). Most patients were male (53.1 %), experienced anterior circulation large-vessel occlusion (81.8 %), and underwent endovascular thrombectomy by stent retreiver (70.7 %). The primary outcome was change in National Institutes of Health Stroke Scale score from presentation to 24 h after thrombectomy. Secondary outcomes included modified Rankin scale score improvement and 90-day score, recanalization rates, procedural complications, and mortality rates. After treatment, 88.5% of children had successful recanalization; the mean National Institutes of Health Stroke Scale score reduction was 7.37 (95 % CI 5.11-9.63, p < 0.01). The mean reduction of 6.87 (95 %CI 5.00-8.73, p < 0.01) for adults in 5 clinical trials (n = 634) was similar (Qb = 0.11; p = 0.74). Children experienced higher rates of good neurological outcome (76.1 % vs. 46.0 %, p < 0.01) and revascularization (88.5 % vs. 72.3 %, p < 0.01), fewer major periprocedural complications (3.6 % vs. 30.4 %, p < 0.01), and lower mortality (1.0 % vs. 12.9 %, p < 0.01). CONCLUSIONS: Endovascular thrombectomy may be safe and effective treatment for acute ischemic stroke due to large-vessel occlusion in children. The aggregated data demonstrated high rates of revascularization, favorable long-term neurological outcomes, and low complication rates.

Humoral Response After Two Doses of COVISHIELDTM Vaccine in Patients Undergoing Maintenance Hemodialysis.

OBJECTIVES: Maintenance hemodialysis (MHD) patients are at increased risk of contracting coronavirus disease 2019 (COVID-19). Vaccine against COVID-19 offers the benefit of protection from severe illness. In this study, we assessed the humoral response after two doses of the COVISHIELDTM vaccine in MHD patients. MATERIALS AND METHODS: In a prospective cohort study, the humoral response with two doses of the COVISHIELDTM vaccine was assessed after 14 ± 2 days of the second dose. The COVIPROTECT antibody titers against the spike protein were measured using the electrochemiluminescence immunoassay (ELECSYS, Roche Diagnostics International Ltd.). Data were analyzed to determine the predictors of antibody response. RESULTS: Between February and October 2021, 50 MHD patients were assessed. The mean age was 55.8 ± 10.8 years, and 72% were males. A total of 48 (96%) MHD patients have seropositivity. The median level of spike protein antibody was 579 U/mL [interquartile range (IQR25-75) 166-1852.75]. Compared to patients with no COVID-19 infection history, the median levels of antibodies were significantly higher in those with a history of COVID-19 (1047 vs 297 U/mL, p = 0.011). The antibody titers did not differ by age (p = 0.269), presence of comorbidities such as hypertension (p = 0.341), diabetes mellitus (p = 0.719) or ischemic heart disease (IHD) (p = 0.695), dialysis vintage (p = 0.660), and timing of diagnosis of COVID-19 in relation to vaccination (p = 0.261). Adverse events (AEs) occurred in one-third of patients that were mild and self-limiting. No serious AEs were observed in any patient. CONCLUSION: In MHD patients, two doses of the COVISHIELDTM vaccine induced a substantial humoral response. Prior history of COVID-19 resulted in a higher antibody response. Thus, the COVISHIELDTM vaccine is efficacious and safe for use in patients with MHD. How to cite this article: Balwani MR, Pasari AS, Bawankule C, et al. Humoral Response After Two Doses of COVISHIELDTM Vaccine in Patients Undergoing Maintenance Hemodialysis. J Assoc Physicians India 2023;71(9):56-60.

How Flexible Is the Concept of Local Thermodynamic Equilibrium?

It has been demonstrated by using generalized phenomenological irreversible thermodynamic theory (GPITT) that by replacing the conventional composition variables {xk} by the quantum level composition variables {x˜k,j} corresponding to the nonequilibrium population of the quantum states, the resultant description remains well within the local thermodynamic equilibrium (LTE) domain. The next attempt is to replace the quantum level composition variables by their respective macroscopic manifestations as variables. For example, these manifestations are, say, the observance of fluorescence and phosphorescence, existence of physical fluxes, and ability to register various spectra (microwave, IR, UV-VIS, ESR, NMR, etc.). This exercise results in a framework that resembles with the thermodynamics with internal variables (TIV), which too is obtained as a framework within the LTE domain. This TIV-type framework is easily transformed to an extended irreversible thermodynamics (EIT) type framework, which uses physical fluxes as additional variables. The GPITT in EIT version is also obtained well within the LTE domain. Thus, GPITT becomes a complete version of classical irreversible thermodynamics (CIT). It is demonstrated that LTE is much more flexible than what CIT impresses upon. This conclusion is based on the realization that the spatial uniformity for each tiny pocket (cell) of a spatially non-uniform system remains intact while developing GPITT and obviously in its other versions.

Prognostic and predictive roles of cancer stem cell markers in head and neck squamous cell carcinoma patients receiving chemoradiotherapy with or without nimotuzumab.

BACKGROUND: Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are needed to identify the patients most likely to benefit from these therapies. Here, we present predictive and prognostic associations of different cancer stem cell markers in HPV-negative locally advanced (LA) HNSCC patients. METHODS: Pretreatment tumour tissues of 404 HPV-negative LA-HNSCCs patients, a subset of-phase 3-randomised study comparing cisplatin-radiation(CRT) and nimotuzumab plus cisplatin-radiation(NCRT) were examined. The expression levels of CD44, CD44v6, CD98hc, ALDH1A1, SOX2 and OCT4A were evaluated using immunohistochemistry. Progression-free survival(PFS), loco-regional control(LRC),- and overall survival(OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. RESULTS: NCRT showed significantly improved OS with low membrane expression of CD44 compared to CRT [HR (95% CI) = 0.63 (0.46-0.88)]. Patients with low CD44v6 also showed better outcomes with NCRT [LRC: HR (95% CI) = 0.25 (0.10-0.62); OS: HR (95% CI) = 0.38 (0.19-0.74)]. No similar benefit with NCRT observed in patients with high CD44 or CD44v6 expression. Bootstrap resampling confirmed the predictive effect of CD44 (Interaction P = 0.015) and CD44v6 (Interaction P = 0.041) for OS. Multivariable Cox analysis revealed an independent negative prognostic role of CD98hc membrane expression for LRC [HR (95% CI) = 0.63(0.39-1.0)] and OS[HR (95% CI) = 0.62 (0.40-0.95)]. CONCLUSIONS: CD44 and CD44v6 are potential predictive biomarkers for NCRT response. CD98hc emerged as an independent negative prognostic biomarker. CLINICAL TRIAL REGISTRATION: Registered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).

Analysis of 3-O-Sulfated Heparan Sulfate Using Isotopically Labeled Oligosaccharide Calibrants.

The 3-O-sulfated glucosamine in heparan sulfate (HS) is a low-abundance structural component, but it is a key saccharide unit for the biological activities of HS. A method to determine the level of 3-O-sulfated HS is lacking. Here, we describe a LC-MS/MS based method to analyze the structural motifs. We determined the levels of 3-O-sulfated structural motifs from pharmaceutical heparin manufactured from bovine, porcine, and ovine. We discovered that saccharide chains carrying 3-O-sulfation from enoxaparin, an FDA-approved low-molecular weight heparin, displayed a slower clearance rate than non-3-O-sulfated sugar chains in a mouse model. Lastly, we detected the 3-O-sulfated HS from human brain. Furthermore, we found that a specific 3-O-sulfated structural motif, tetra-1, is elevated in the brain HS from Alzheimer's disease patients (n = 5, p = 0.0020). Our method offers a practical solution to measure 3-O-sulfated HS from biological sources with the sensitivity and quantitative capability.

Current Controversies in Radiology on Cost, Reimbursement, and Price Transparency: AJR Expert Panel Narrative Review.

Many believe that fundamental reform of the U.S. health care system is overdue and necessary given rising national health care expenditures, poor performance on key population health metrics, meaningful health disparities, concerns about potential financial toxicity of care, inadequate price transparency, pending insolvency of Medicare Part A, increasing commercial insurance premiums, and large uninsured and underinsured populations. The Medicare Payment Advisory Commission, an independent congressional agency, believes that part of this reform includes redistribution of reimbursements away from specialties such as radiology. Thus, despite an increase in the Medicare population and spending, Medicare payments for medical imaging have been decreasing for years. Further, the No Surprises Act, a federal law intended to curb the problem of surprise medical billing, was repurposed in federal rulemaking to reduce reimbursement from commercial payers to certain specialties, including radiology. In this article, we examine challenges facing the U.S. health care system, focusing on cost, reimbursement, and price transparency and the role of radiology in addressing such challenges. Medical imaging is a minor contributor to national health care expenditures but has an outsized impact on patient care. The radiology community should work together to reinforce the value of medical imaging and reduce inappropriate utilization of low-value care.