Laser processing of sapphire and fabrication of diffractive optical elements.

Sapphire is a high-temperature optical material with a melting temperature of over 2000ºC, high strength, good thermal conductivity, and low thermal expansion, and it exhibits chemical inertness and is optically transparent over a wavelength range of 0.15 µm to 5.5 µm. We report the detailed results of the laser processing of sapphire, fabrication of diffraction gratings, and the photon sieve, which have applications in the infrared spectrum using a nanosecond pulsed laser of 355 nm wavelength. Laser removal rates and surface roughness were studied. The fabricated gratings and photon sieve were characterized in terms of diffracted beam profile, optical diffraction efficiency, surface morphology, and depth profile.

Diagnosis of osteoarticular tuberculosis by immuno-PCR assay based on mycobacterial antigen 85 complex detection.

Diagnosis of osteoarticular tuberculosis (OATB) exhibits serious challenges owing to paucibacillary nature of specimens and localization of disease at sites that are difficult to access. We recently developed indirect immuno-PCR (I-PCR) and real-time I-PCR (RT-I-PCR) assays for the detection of mycobacterial antigen 85 complex (Ag85) in OATB patients. Detection limits for the purified Ag85 protein were found to be 1 and 41 fg ml-1 by I-PCR and RT-I-PCR, respectively, which were at least 105 -fold lower than respective ELISA. While spiking synovial fluids of non-TB control subjects with the purified Ag85 protein, LODs of 100 and 120 fg ml-1 were obtained by I-PCR and RT-I-PCR, respectively, thus demonstrating the sample matrix effect. Sensitivities of 87·5 and 70·5% were observed in bodily fluids of confirmed (n = 8) and clinically suspected (n = 51) OATB cases, respectively, by I-PCR, with a specificity of 93·9% (n = 33). Markedly, the sensitivities obtained by I-PCR/RT-I-PCR were significantly higher (P < 0·05-0·01) than ELISA and GeneXpert assay (n = 30). However, no substantial difference in sensitivity was observed between the I-PCR and RT-I-PCR assays. After further improving the accuracy of I-PCR, this test may lead to development of an attractive diagnostic kit.

Zolpidem for Insomnia: A Double-Edged Sword. A Systematic Literature Review on Zolpidem-Induced Complex Sleep Behaviors.

BACKGROUND: Being a nonbenzodiazepine, zolpidem is believed to have a favorable side-effect profile and is widely prescribed for insomnia. However, in the past few years, numerous neuropsychiatric adverse reactions, particularly complex sleep behaviors (CSBs), have been reported with zolpidem. OBJECTIVE: To conduct a systematic review of zolpidem-associated CSBs. DATA SOURCES: An electronic search was conducted using MEDLINE, Embase, PubMed, and Cochrane database of systematic reviews to extract relevant articles till July 2020. STUDY ELIGIBILITY CRITERIA: Any type of literature article (case report, case series, and observational or interventional study) reporting CSBs associated with zolpidem. RESULTS: In this review, we present aggregate summarized data from 148 patients presenting with zolpidem-induced CSBs (79 patients from 23 case reports and 5 case series; 69 patients out of 1454 taking zolpidem [4.7%] from three observational clinical studies). Various types of CSBs associated with zolpidem were reported, most common being sleepwalking/somnambulism and sleep-related eating disorder. On causality assessment, around 88% of cases were found to have a probable association with zolpidem. LIMITATIONS: Extraction of data from observational studies and spontaneous reports, due to nonavailability of any randomized controlled trials relevant to the study objective. CONCLUSION AND IMPLICATION OF KEY FINDINGS: Zolpidem-induced CSBs, although not very common, may develop when the drug is used at therapeutic doses for insomnia. Doctors need to be alert to monitor such adverse effects of zolpidem and exercise caution while prescribing it.

Systematic review and meta-analysis of efficacy and safety of hydroxychloroquine and chloroquine in the treatment of COVID-19.

Repurposed drugs like hydroxycloroquine (HCQ) and chloroquine (CQ) are being tested for potential therapeutic role in COVID-19. We aimed to evaluate efficacy and safety of HCQ and CQ in COVID-19. Using PubMed, EMBASE, medRxiv, Google Scholar, clinicaltrials.gov, electronic search was carried out to identify relevant articles till June 2020 with re-evaluation in last week of November 2020. Observational and interventional clinical studies comparing efficacy of CQ or HCQ to standard management or other drug/s for SARS-CoV-2 infection patients were included. Cochrane review manager version 5.3 was used for synthesis of meta-analysis results. For randomized controlled trials, risk of bias was assessed using Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). ROBINS-I was used for quality assessment of observational studies. Overall evidence quality generated by review was graded as per GRADE Recommendation. A total of 903 studies were screened. Nineteen studies were included in synthesis of meta-analysis with total of 4,693, 1,626, and 6,491 patients in HCQ/CQ, HCQ/CQ + AZ and control groups, respectively. HCQ/CQ treatment was associated with significantly increased rates of virological cure (OR = 2.08, 95%CI = 1.36-3.17; P = 0.0007) and radiological cure (OR = 3.89, 95%CI = 1.35 - 11.23; P = 0.01) compared to control. HCQ/CQ had no difference in unadjusted mortality rate (unadjusted OR = 0.98 95% CI = 0.70-1.37, P = 0.89, random effect model) and adjusted hazard ratio for mortality (adjusted HR = 1.05, 95%CI = 0.86--1.29; P = 0.64). However, a significant increase in odds of disease progression (OR = 1.77, 95%CI = 1.46-2.13; P < 0.00001) and QT prolongation (OR = 11.15, 95%CI = 3.95-31.44; P < 0.00001) was noted. The results with HCQ/CQ and azithromycin combination were similar to HCQ/CQ mono-therapy. In the light of contemporary evidence on effectiveness of HCQ/CQ, judicious and monitored use of HCQ/CQ for treatment of COVID-19 patients is recommended in low to middle income countries with emphasis on no mortality benefit. Registration number of Systematic review. Register in PROSPERO database: cRD42020187710.

Human occupation of northern India spans the Toba super-eruption ~74,000 years ago.

India is located at a critical geographic crossroads for understanding the dispersal of Homo sapiens out of Africa and into Asia and Oceania. Here we report evidence for long-term human occupation, spanning the last ~80 thousand years, at the site of Dhaba in the Middle Son River Valley of Central India. An unchanging stone tool industry is found at Dhaba spanning the Toba eruption of ~74 ka (i.e., the Youngest Toba Tuff, YTT) bracketed between ages of 79.6 ± 3.2 and 65.2 ± 3.1 ka, with the introduction of microlithic technology ~48 ka. The lithic industry from Dhaba strongly resembles stone tool assemblages from the African Middle Stone Age (MSA) and Arabia, and the earliest artefacts from Australia, suggesting that it is likely the product of Homo sapiens as they dispersed eastward out of Africa.

A digital, constant-frequency pulsed phase-locked-loop instrument for real-time, absolute ultrasonic phase measurements.

A digitally controlled instrument for conducting single-frequency and swept-frequency ultrasonic phase measurements has been developed based on a constant-frequency pulsed phase-locked-loop (CFPPLL) design. This instrument uses a pair of direct digital synthesizers to generate an ultrasonically transceived tone-burst and an internal reference wave for phase comparison. Real-time, constant-frequency phase tracking in an interrogated specimen is possible with a resolution of 0.000 38 rad (0.022°), and swept-frequency phase measurements can be obtained. Using phase measurements, an absolute thickness in borosilicate glass is presented to show the instrument's efficacy, and these results are compared to conventional ultrasonic pulse-echo time-of-flight (ToF) measurements. The newly developed instrument predicted the thickness with a mean error of -0.04 µm and a standard deviation of error of 1.35 µm. Additionally, the CFPPLL instrument shows a lower measured phase error in the absence of changing temperature and couplant thickness than high-resolution cross-correlation ToF measurements at a similar signal-to-noise ratio. By showing higher accuracy and precision than conventional pulse-echo ToF measurements and lower phase errors than cross-correlation ToF measurements, the new digitally controlled CFPPLL instrument provides high-resolution absolute ultrasonic velocity or path-length measurements in solids or liquids, as well as tracking of material property changes with high sensitivity. The ability to obtain absolute phase measurements allows for many new applications than possible with previous ultrasonic pulsed phase-locked loop instruments. In addition to improved resolution, swept-frequency phase measurements add useful capability in measuring properties of layered structures, such as bonded joints, or materials which exhibit non-linear frequency-dependent behavior, such as dispersive media.

The effect of noggin interference in a rabbit posterolateral spinal fusion model.

STUDY DESIGN: Noggin protein levels and spinal fusion rates were compared in a rabbit model after application of siRNA against BMP antagonist noggin in paraspinal muscle. OBJECTIVE: To test whether endogenous BMPs are sufficient to form bone in the absence of their antagonists, using noggin siRNA to interrupt the negative feedback loop on endogenous BMP within the paraspinal muscles in rabbits. Unused Posterolateral lumbar fusion is a standard surgical treatment for many spinal disorders, yet even under ideal conditions the rate of non-fusion approaches 25 %. BMPs are effective in promoting bone formation, and are inhibited by antagonists such as noggin. We have previously shown that in this model, endogenous BMPs are present and endogenous BMP antagonist noggin is strongly increased during spinal fusion. Previous studies have found that noggin siRNA enhanced spinal fusion in combination with supra-physiological amounts of exogenous BMP; however, the effect of the siRNA alone remains unknown. METHODS: A posterolateral intertransverse rabbit lumbar fusion was utilized, as established by Boden et al. SiRNA against noggin was electroporated into paraspinal muscle to determine its effect on fusion. Outcome measures included noggin protein expression, and assessment of spinal fusion at 6 weeks. RESULTS: SiRNAs were effective in reducing overexpressed noggin in vitro. Noggin protein was successfully knocked down in vivo for the initial 7 days in our rabbit model and returned to detectable levels by 4 weeks and to normal levels by 6 weeks. The overall fusion rate was not significantly enhanced compared to established controls from our earlier work (Tang et al.). CONCLUSIONS: Early noggin suppression does not appear to enhance the BMP activity sufficiently to significantly affect final fusion rates in our model.

Generativity, hierarchical action and recursion in the technology of the Acheulean to Middle Palaeolithic transition: a perspective from Patpara, the Son Valley, India.

The Acheulean to Middle Palaeolithic transition is one of the most important technological changes that occurs over the course of human evolution. Here we examine stone artefact assemblages from Patpara and two other excavated sites in the Middle Son Valley, India, which show a mosaic of attributes associated with Acheulean and Middle Palaeolithic industries. The bifaces from these sites are very refined and generally small, but also highly variable in size. A strong relationship between flake scar density and biface size indicates extensive differential resharpening. There are relatively low proportions of bifaces at these sites, with more emphasis on small flake tools struck from recurrent Levallois cores. The eventual demise of large bifaces may be attributed to the curation of small prepared cores from which sharper, or more task-specific flakes were struck. Levallois technology appears to have arisen out of adapting aspects of handaxe knapping, including shaping of surfaces, the utilization of two inter-dependent surfaces, and the striking of invasive thinning flakes. The generativity, hierarchical organization of action, and recursion evident in recurrent Levallois technology may be attributed to improvements in working memory.

Critical appraisal of the existing and emerging therapies for smoking cessation.

Smoking is a major health problem of the society as it causes a wide variety of health hazards and produces a strong addictive behavior. Various pharmacological and non pharmacological treatments have been tried for smoking cessation from time to time. Some of the pharmacological treatments have been able to achieve the status of first line and second line therapy for smoking cessation by the US Public Health Service Clinical Practice Guideline. Some newer and very promising drugs have come up and are in the clinical trials for establishment of their efficacy. While some other drugs have been tried from time to time but have failed to show any consistent results. Various non pharmacological therapies like behavioural therapy are also of utmost importance in this regard. This article gives a brief review and critical assessment of the existing and the emerging smoking cessation therapies.

Clinical evaluation of two antiemetic combinations palonosetron dexamethasone versus ondansetron dexamethasone in chemotherapy of head and neck cancer.

INTRODUCTION: Palonosetron and ondansetron are two selective 5-hydroxytryptamine (5-HT3) receptor antagonists that have shown remarkable efficacy in controlling nausea and vomiting following administration of moderately emetic anticancer chemotherapy. Their efficacy is enhanced by the concurrent administration of dexamethasone. In the present study, we aimed to compare the antiemetic efficacy of a palonosetron plus dexamethasone (PD) schedule versus an ondansetron plus dexamethasone (OD) schedule. METHODS: A randomised, crossover trial was conducted in 30 patients with head and neck cancer who were receiving moderately emetogenic chemotherapy. The patients were divided into two groups. In the first cycle, one group was given a PD schedule and the other, an OD schedule. For the subsequent cycle, crossover of the antiemetic schedules was done. The antiemetic effects were evaluated by recording the intensity of nausea and the frequency of vomiting in the acute and delayed phases. RESULTS: Complete response in the acute phase was observed in 83.3 percent of the patients on the PD schedule and in 80 percent of those on the OD schedule. In the delayed phase, complete response was observed in 76.7 percent and 66.7 percent of the patients on the PD schedule and OD schedule, respectively. The overall rate of complete response was 66.7 percent in the PD group and 46.7 percent in the OD group. In the PD group, there were 73.3 percent of nausea-free patients as opposed to 66.7 percent in the OD group. CONCLUSION: The results suggest that the PD schedule was superior to the OD schedule in controlling emesis in cancer chemotherapy, although this difference was not statistically significant.

Femtosecond holographic interferometry for studies of semiconductor ablation using vanadium dioxide film.

A recording medium based on the phenomenon of phase transition from semiconductor to metal is applied to holography in the femtosecond time domain. The results of holographic interferometry studies of semiconductor ablation are presented.

Effect of nimodipine, a dihydropyridine calcium channel antagonist on the pharmacokinetics of carbamazepine in rhesus monkeys.

Calcium channel antagonists have been shown to have an anticonvulsant activity in a variety of seizure models and also to potentiate the anticonvulsant activity of other standard antiepileptic drugs like carbamazepine, phenytoin and valporoate. A pharmacokinetic interaction may be involved in such potentiation. This cross over single dose study was carried out to find out if there was a pharmacokinetic interaction between carbamazepine, a commonly used antiepileptic drug and nimodipine, a dihydropyridine calcium channel antagonist in rhesus moneys. Carbamazepine 46 mg/kg and nimodipine 9.6 mg/kg was administered through a nasogastric tube and blood samples were collected at 0.5, 1, 2, 3, 6, 9, 12, 24, 48, 72 and 96 hours after drug administration and were assayed for carbamazepine. Nimodipine caused a significant increase in peak plasma concentration (C(max)) of carbamazepine and a decrease in plasma absorption half life (t1/2 alpha). There was no significant change in other pharmacokinetic parameters between the two groups. The results of the study suggest that concurrent administration of carbamazepine and nimodipine may cause a significant rise in carbamazepine concentration as may contribute to a potentiation of anticonvulsant effect of carbamazepine and an increase in the incidence of adverse effects warranting that nimodipine should be prescribed cautiously in epileptic patients receiving carbamazepine and it might be very appropriate to do therapeutic drug monitoring of carbamazepine in such patients.

The use of neostigmine to treat postoperative ileus in orthopedic spinal patients.

Ileus is a common complication of spinal surgery, affecting 5% to 12% of all patients. Often this ileus is secondary to acute colonic pseudo-obstruction. This study is a prospective clinical trial of neostigmine in seven spinal patients with ileus after surgery to demonstrate its efficacy. All patients had evidence of the Ogilvie syndrome that was unresponsive to 24 hours of conservative therapy. Patients received 2 mg neostigmine, and abdominal circumference, clinical response, and radiographic colonic measurements were recorded. Patients were followed for recurrence of ileus for their remaining time in the hospital. Six patients had prompt colonic decompression, and no patient had recurrence of colonic distension. Side effects were minimal. These results suggest that postoperative spinal patients with ileus secondary to acute colonic pseudo-obstruction that is unresponsive to conservative therapy benefit from treatment with neostigmine, resulting in safe, rapid decompression of the colon.

The role of acute decompression and restoration of spinal alignment in the prevention of post-traumatic syringomyelia: case report and review of recent literature.

STUDY DESIGN: Case report. INTRODUCTION: Acute post-traumatic syringomyelia formation after spinal cord injury has been considered a rare complication. At this writing, most recent reports have surfaced in neurosurgical journals. As an entity, post-traumatic syringomyelia has not been widely appreciated. It has been confused with conditions such as Hansen's disease or ulnar nerve compression at the cubital tunnel. One study also demonstrated that the occurrence of syrinx is significantly correlated with spinal stenosis after treatment, and that an inadequate reduction of the spine may lead to the formation of syrinx. This reported case describes a patient in whom post-traumatic syringomyelia began to develop 3 weeks after injury, which improved neurologically after adequate decompression. SUMMARY OF BACKGROUND DATA: A 30-year-old man sustained a 20-foot fall at work. He presented with a complete spinal cord injury below T4 secondary to a T4 fracture dislocation. The patient underwent open reduction and internal fixation of T1-T8. After 3 weeks, the patient was noted to have ascending weakness in his bilateral upper extremities and some clawing of both hands. METHODS: A computed tomography myelogram demonstrated inability of contrast to pass through the T4-T5 region from a lumbar puncture. An incomplete reduction was noted. The canal showed significant stenosis. A magnetic resonance image of the patient's C-spine showed increased signal in the substance of the cord extending into the C1-C2 area. The patient returned to the operating room for T3-T5 decompressive laminectomy and posterolateral decompression including the pedicles, disc, and posterior aspect of the body. Intraoperative ultrasound monitoring showed a good flow of cerebrospinal fluid past the injured segment. RESULTS: On postoperative day 1, the clawing posture of the patient's hands was significantly diminished, and the patient noted an immediate improvement in his hand and arm strength. Over the next few days, the patient's strength in the bilateral upper extremities increased to motor Grade 4/5 on manual testing. A magnetic resonance image 4 weeks after decompression showed significant improvement in the cord diameter and signal. CONCLUSIONS: Post-traumatic syringomyelia has not been reported at so early a stage after injury. This disorder is an important clinical entity that must be recognized to prevent potentially fatal or devastating complications. As evidenced by the reported patient and the literature, if this disorder is discovered and treated early, permanent deficit can be avoided. The prevention of post-traumatic syringomyelia requires anatomic realignment and stabilization of the spine without stenosis, even in the case of complete injuries, to maintain the proper dynamics of cerebrospinal fluid flow.

S1 screw bending moment with posterior spinal instrumentation across the lumbosacral junction after unilateral iliac crest harvest.

STUDY DESIGN: A biomechanical study comparing fixation across the lumbosacral junction. OBJECTIVES: To determine which long posterior construct across the lumbosacral junction produces the least bending moment on the S1 screw when only one ilium is available for fixation. SUMMARY OF BACKGROUND DATA: Recent in vitro studies have demonstrated the benefit of anterior support and fixation into the ilium when instrumenting a long posterior construct across the lumbosacral junction. METHODS: Four L2-sacrum constructs were tested on six synthetic models of the lumbar spine and pelvis simulating that the right ilium had been harvested. Construct 1: L2-S1 bilateral screws. Construct 2: L2-S1 + left iliac bolt. Construct 3: L2-S1 + left iliac bolt + right S2 screw. Construct 4: L2-S1 + bilateral S2 screws. The four constructs were then retested with an anterior L5-S1 strut. A flexion-extension moment was applied across each construct, and the moment at the left and right S1 pedicle screw was measured with internal strain gauges. RESULTS: Iliac bolt fixation was found to significantly decrease the flexion-extension moment on the ipsilateral S1 screw by 70% and the contralateral screw by 26%. An anterior L5-S1 strut significantly decreased the S1 screw flexion-extension moment by 33%. Anterior support at L5-S1 provided no statistical decrease in the flexion-extension moment when bilateral posterior fixation beyond S1 was present with either a unilateral iliac bolt and contralateral S2 screw, or bilateral S2 screws. CONCLUSIONS: There is a significant decrease in the flexion-extension moment on the S1 screw when extending long posterior constructs to either the ilium or S2 sacral screw. There is no biomechanical advantage of the iliac bolt over the S2 screw in decreasing the moment on the S1 screw in flexion and extension. Adding anterior support to long posterior constructs significantly decreases the moment on the S1 screw. Adding distal posterior fixation to either the ilium or S2 decreases the moment on S1 screws more than adding anterior support. Further, adding anterior support when bilateral distal fixation past S1 is already present does not significantly decrease the moment on the S1 screws in flexion and extension.

Influence of kinnow juice on the pharmacokinetics of sustained release theophylline in healthy male volunteers.

The effect of kinnow juice on the pharmacokinetics of a single dose of sustained release theophylline was investigated in healthy male volunteers. In a two phased open cross-over randomized study, ten healthy male volunteers were given sustained release theophylline (300 mg) along with 300 ml of water or kinnow juice, a routinely used citrus juice in India. Blood samples were collected at different time points from 0-48 hours. Plasma was assayed for theophylline by a HPLC method and various pharmacokinetic parameters were calculated and compared. The theophylline levels were lower at all the time points with kinnow juice co-administration as compared to water but were significantly so only during the absorption phase from 1-4 hours. The values for all the pharmacokinetic parameters evaluated were on the lower side with kinnow juice except Tmax which was slightly delayed. None of these alterations was found to be significantly different. The results indicate that since there is an interference with the absorption of the drug, the patients may be advised not to consume kinnow juice when taking a slow release theophylline preparation and the monitoring of plasma concentrations of theophylline in patients who routinely consume kinnow juice in their diet might be helpful in better management of these patients.

Effect of nimodipine, a dihydropyridine calcium channel antagonist, on the steady state pharmacokinetics of phenytoin (DPH) in rhesus monkeys.

Nimodipine, a dihydropyridine calcium channel blocker, has been shown to cause a potentiation of anticonvulsant action of phenytoin (DPH) against maximal electroshock-induced seizures in rats. This crossover study was carried out in rhesus monkeys to determine if any pharmacokinetic interaction was involved in such a potentiation. The steady state pharmacokinetics of phenytoin was examined before and after nimodipine administration. No significant differences were observed in plasma concentration of phenytoin at different time points nor in any of the pharmacokinetic parameters in the two groups. The results reveal that the potentiation of anticonvulsant action of phenytoin by nimodipine is probably due to a pharmacodynamic interaction between the two drugs.

Effect of grapefruit juice on the pharmacokinetics of theophylline in healthy male volunteers.

The effect of grapefruit juice (GFJ) on the pharmacokinetics of a single dose of theophylline was examined in an open crossover study. Healthy male volunteers were given sustained release theophylline (300 mg) along with 300 ml of either water or GFJ. Blood samples (2 ml) were collected at different time points from 0 to 48 h. Plasma was assayed for theophylline by HPLC and various pharmacokinetic parameters were calculated. Theophylline levels were lower at all time points with GFJ coadministration as compared to water but were significantly lower only during the absorption phase from 1 to 4 h. Although the pharmacokinetic parameters were not significantly different between the two groups, all values were reduced except Tmax which was slightly increased. The results indicate that patients may be advised not to consume GFJ when taking slow-release theophylline and monitoring of plasma theophylline levels in patients consuming GFJ might be helpful in better management of patient care.

Type IV collagen is detectable in most, but not all, basement membranes of Caenorhabditis elegans and assembles on tissues that do not express it.

Type IV collagen in Caenorhabditis elegans is produced by two essential genes, emb-9 and let-2, which encode alpha1- and alpha2-like chains, respectively. The distribution of EMB-9 and LET-2 chains has been characterized using chain-specific antisera. The chains colocalize, suggesting that they may function in a single heterotrimeric collagen molecule. Type IV collagen is detected in all basement membranes except those on the pseudocoelomic face of body wall muscle and on the regions of the hypodermis between body wall muscle quadrants, indicating that there are major structural differences between some basement membranes in C. elegans. Using lacZ/green fluorescent protein (GFP) reporter constructs, both type IV collagen genes were shown to be expressed in the same cells, primarily body wall muscles, and some somatic cells of the gonad. Although the pharynx and intestine are covered with basement membranes that contain type IV collagen, these tissues do not express either type IV collagen gene. Using an epitope-tagged emb-9 construct, we show that type IV collagen made in body wall muscle cells can assemble into the pharyngeal, intestinal, and gonadal basement membranes. Additionally, we show that expression of functional type IV collagen only in body wall muscle cells is sufficient for C. elegans to complete development and be partially fertile. Since type IV collagen secreted from muscle cells only assembles into some of the basement membranes that it has access to, there must be a mechanism regulating its assembly. We propose that interaction with a cell surface-associated molecule(s) is required to facilitate type IV collagen assembly.