Hydrocephalus associated with a molar tooth sign: A distinct subtype of Joubert syndrome.

Hydrocephalus is rarely described in Joubert-Boltshauser syndrome (JBTS). The aim of this study was to investigate whether this association is a chance occurrence or potentially signifies a new phenotypic subtype. The databases of Wolfson Medical Center, Sourasky Medical Center, and EB's personal collection were reviewed. Records from an additional family were obtained from RG. The patients' medical records, prenatal ultrasounds, and magnetic resonance imaging were assessed. In addition, we reviewed the medical literature for the association of ventriculomegaly/hydrocephalus (VM/HC) in JBTS. Only seven cases (from five families) were found with prenatal onset of VM/HC, diagnosed during the second trimester; three pregnancies were terminated, one was stillborn and three were born, of which one died within a week, and another died at the age of 6 years. Additional central nervous system findings included dysgenesis of the corpus callosum, delayed sulcation, polymicrogyria, and pachygyria. We found 16 publications describing 54 patients with JBTS and VM/HC: only five were diagnosed at birth and three were diagnosed prenatally. Hydrocephalus is extremely rare in JBTS. The recurrence of this association, reported in several publications in multiple family members, suggests that it might represent a new phenotypic subtype of JBTS possibly associated with specific genes or variants. Further genetic studies are needed to confirm this hypothesis. WHAT THIS PAPER ADDS: The association of fetal hydrocephalus with Joubert-Boltshauser syndrome (JBTS) is very rare but not a chance association. This association represents a new phenotypic subtype of JBTS possibly linked to specific genes or variants.

Spectrum of fetal limb anomalies.

PURPOSE: Antenatal detection of limb anomalies is not uncommon, and pregnancies are usually terminated in view of the expected physical handicap. The aim of this retrospective observational study is to delineate the spectrum of fetal limb anomalies and provide evidence in support of complete postnatal evaluation in establishing recurrence risk. METHODS: We present 54 cases of limb malformations detected antenatally and discuss the spectrum of abnormalities, the utility of fetal autopsy, and genetic testing to establish recurrence risk in subsequent pregnancies. RESULTS: 16/54 cases were isolated radial ray anomalies. There were five cases of amniotic band syndrome, five limb body wall complex cases, three VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) associations, one case of sirenomelia, two cases of limb pelvis hypoplasia, and one case of OEIS (Omphalocele Exstrophy Imperforate anus and spinal defects). Four fetuses with non-isolated radial ray anomaly had trisomy 18. One case with bilateral radial ray defect had a mutation in the FANC-E gene confirming fanconi anemia. Twelve cases were unclassified. CONCLUSION: Autopsy is the most important investigation in fetuses with limb anomalies. We suggest chromosomal microarray (CMA) as a first-tier test after autopsy. However, in cases of bilaterally symmetrical limb anomalies, in case of previous similarly affected child, or history of consanguinity, whole exome sequencing (WES) can be offered as the primary investigation, followed by CMA if WES is normal.

Increased Pill Burden and Adverse Effects of Psychotropics Correlated with Poor Quality of Life and Medication Nonadherence: A Cross-sectional Drug Utilization Study at a Tertiary Care Hospital in Delhi during COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to an increase in mental health problems such as depression and anxiety. This study aims to investigate the prescribing pattern of psychotropic drugs in patients with common mental disorders which might be altered during the pandemic and also whether the pandemic could alter their quality of life (QOL) and medication adherence. MATERIALS AND METHODS: After prior ethical approval, a descriptive cross-sectional drug utilization study (DUS) of 200 prescriptions was undertaken to evaluate the pattern of psychotropic drug usage as per WHO (World Health Organization)/International Network of Rational Use of Drugs (INRUD) guidelines. The correlation of the average number of drugs per prescription with QOL was observed. The correlation of adverse drug reactions (ADRs) with medication adherence was also analyzed. RESULTS: The average number of drugs per prescription during the pre-COVID-19 and COVID-19 period was estimated to be 2.48 and 2.96. The percentage of drugs prescribed by generic name in the two different periods (pre-COVID-19 and COVID-19) was 97.40 and 95.77%. The percentage of drugs prescribed from the list of essential medicines was 89.40 and 85.12%, respectively. The percentage of prescriptions with injections was 0.45% and 0.53%, respectively for the two periods. The QOL during the COVID-19 pandemic was found to be negatively correlated to the average number of drugs per prescription (correlation coefficient = -0.61) and medication adherence was found to be poor in patients who developed ADRs with the drugs prescribed (p-value of 0.001). CONCLUSION: In the tertiary care hospital described, rational drug prescribing was followed. Increase in the number of drugs per prescription was found to be associated with poor QOL and the development of ADRs led to medication nonadherence in the patients. Further studies with larger sample sizes are needed to confirm these results. How to cite this article: Kumar A, Halder S, Srivastava S, et al. Increased Pill Burden and Adverse Effects of Psychotropics Correlated with Poor Quality of Life and Medication Nonadherence: A Cross-sectional Drug Utilization Study at a Tertiary Care Hospital in Delhi during COVID-19 Pandemic. J Assoc Physicians India 2023;71(9):14-18.

Sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation in MDD patients with moderate to severe depression and effect on inflammatory markers.

BACKGROUND: This study evaluated the effect of sertraline with desvenlafaxine and sertraline with mirtazapine on HAM-D score and inflammatory markers (IL-6 and TNF-α levels) in major depressive disorder. METHODS: Patients (18-60 years) with MDD diagnosed by DSM-V criteria and HAM-D score 18 or more were included (n = 60). Group A patients (n = 30) received sertraline 50 mg/day and desvenlafaxine 50 mg/day. Group B patients (n = 30) received sertraline 50 mg/day and mirtazapine 30 mg/day. All patients were followed up for 8 weeks for the evaluation of clinical efficacy, safety, serum IL-6, and TNF-α levels. RESULTS: Our study showed a comparatively similar and statistically significant (p < 0.05) reduction in HAM-D score in both groups in the 4th and 8th week of the treatment. Both drug combinations significantly (p < 0.05) decreased serum IL-6 and TNF-α after 8 weeks of treatment. CONCLUSION: The present study suggests that the combination therapy (as treatment initiation) with sertraline and desvenlafaxine, and sertraline with mirtazapine is effective and well tolerated in MDD patients with moderate to severe depression, and their therapeutic efficacy is accompanied by decreased inflammatory markers (serum IL-6 and TNF-α).

Recent evidence indicates that combination therapy of antidepressant drugs started as treatment initiation produces superior treatment outcomes in patients of MDD with moderate to severe depression.MDD is associated with increased inflammatory markers.Combination therapy of sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation is effective and well tolerated in MDD patients.The therapeutic efficacy of sertraline with desvenlafaxine and sertraline with mirtazapine is associated with a significant decrease in serum levels of IL-6 and TNF-α.

Amyoplasia in monochorionic monozygotic pregnancy following interstitial laser.

Amyoplasia is a specific form of arthrogryposis, without any genetic cause. Six to ten percent of amyoplasia cases are one of the monozygotic twins, with the other twin being normal. Failure of maturation of anterior horn cells (AHCs) due to ischemic injury has been postulated as the primary pathological change, leading to arrest in the development of muscle fibers supplied by the affected AHCs with the typical limb positioning seen in amyoplasia. Twin-to-twin transfusion syndrome (TTTS) is an important risk factor for ischemic injury in monozygotic twin pregnancies. We present a case of monochorionic diamniotic twin pregnancy with features of TTTS at 12 weeks who underwent interstitial laser followed by the development of lower limb akinesia in the surviving fetus. Possible causes of amyoplasia are discussed.

Association of serotonin transporter gene polymorphism with efficacy of the antidepressant drugs sertraline and mirtazapine in newly diagnosed patients with major depressive disorders.

OBJECTIVE: We examined the association of serotonin receptor transporter gene polymorphism in patients with MDD with the clinical efficacy of mirtazapine (MZ) and sertraline (ST). METHOD: Newly diagnosed, treatment naïve, 80 MDD patients (aged 18-45) diagnosed using DSM-5 criteria and with Beck's depression inventory score (BDI) score ≥21 were included and randomly divided into two groups of 40 participants and were administered MZ 15-45 mg/day or ST 25-200 mg/day respectively. Patients were followed up for 6 weeks for evaluation of BDI scores. Genotypic evaluation was done and three allele variants were identified based on the polymerase chain reaction fragment sizes: short (S; 486 bp), long (L; 529 bp), or extralong (XL; 612 or 654 bp) and classified into five genotypes: S/S,S/L, L/L, S/XL, and L/XL. RESULT: We found that 32.5% patients belonged to the S/S genotype, suggesting that individuals with the SS genotype are at higher risk of developing MDD. No statistically significant association was seen with ST or MZ groups on the basis of genotypes. Clinically significant improvement was observed with a more than 50% reduction in BDI scores at 6 weeks of treatment with both drugs. CONCLUSION: Identification of risk population can be carried out by genotype testing. Prior genotyping in MDD patients might help to predict a better clinical outcome with antidepressants.

Neuroinvasion of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2): future risk of epilepsy.

Central nervous system (CNS) infection is one of the important risk factors for epilepsy. COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has primarily been considered to involve respiratory system only, but it can also affect the CNS. A wide range of neurological manifestations have been reported in SARS-CoV-2 infected patients including seizures, status epilepticus, stroke, which are considered as important risk factors for the development of epilepsy. In post-mortem, brain tissue samples of COVID-19 patients have shown neuropathological changes and presence of SARS-CoV-2 RNA and viral proteins. In this review, mechanisms of SARS-CoV-2 neuroinvasion like neuronal retrograde trans-synaptic route and vascular route are described along with important neurological manifestations in COVID-19 patients such as seizures and cerebrovascular diseases, which have been found to be associated with the development of epilepsy. Hence, an increased risk of future burden of epilepsy in susceptible COVID-19 survivors has been proposed and preventive measures are suggested. The present review highlights about the possible association between neurological manifestations and future risk of epilepsy in COVID-19 patients.

Correlation between telomere length and efficacy of oral and long-acting injectable antipsychotics on severity and cognitive impairment of schizophrenia.

OBJECTIVE: To study the correlation between telomere length (TL) and long-acting injectable (LAI) and oral atypical antipsychotic (OAA) efficacy on schizophrenia (SCZ) severity and cognitive impairment. METHODS: Sixty Schizophrenia patients of 18-50 years and of either sex were included in a 12-week study. Thirty patients were recruited in each group, LAI and OAA. Positive and Negative Syndrome Scale (PANSS) and National Institute of Mental Health and Neuro-Sciences (NIMHANS) neuropsychological battery tests were evaluated at baseline and 12 weeks. TL was estimated at baseline. RESULTS: Both groups showed a significant improvement in PANSS and NIMHANS battery test scores after treatment (p < 0.001) within the group, though not between the groups. Mean TL at baseline was 407.58 ± 143.93 and 443.40 ± 178.46 in LAI and OAA groups respectively. A significant negative correlation (r = -0.28, p = 0.03) of TL was seen with the mean change in negative PANSS score after treatment. CONCLUSIONS: LAI antipsychotics are similar to OAA in decreasing the disorder severity and improving the cognitive impairment in schizophrenia. Also, patients who have shorter TL show greater improvement in the negative PANSS score. Hence, TL holds the potential of predicting antipsychotic drug response in schizophrenia patients.KEY POINTSLong-acting injectable antipsychotic was comparable to oral atypical antipsychotics in bringing out improvement in disorder severity, cognitive functions over 12 weeks.Shorter telomere length has been found to be associated with a greater response in negative symptoms of schizophrenia.

Intranasal midazolam versus intravenous/rectal benzodiazepines for acute seizure control in children: A systematic review and meta-analysis.

BACKGROUND: Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a venous line may be difficult in children with seizures which would delay the initiation of treatment. Rectal drug administration can be socially awkward for patients and providers. Intranasal (IN) midazolam offers a valuable substitute that is easier and faster to administer. OBJECTIVE: To assess the efficacy, safety, and acceptability of intranasal midazolam in children with acute seizure when compared to conventional IV or rectal benzodiazepine (BDZ). METHODS: PubMed, google scholar, websites clinicaltrials.gov and the WHO-international clinical trials registry platform, were searched. Randomized controlled/prospective randomized trials comparing IN midazolam against IV/rectal BDZ in the treatment of acute seizures in pediatric patients were included in the meta-analysis. RESULTS: Data of 10 studies were quantitatively analyzed. Intranasal midazolam (n = 169) when compared to IV/rectal BDZ (n = 161) has a shorter interval between hospital arrival and seizure cessation {(mean difference = -3.51; 95% CI [-6.84, -0.18]) P = 0.04}. Regarding time to seizure cessation after midazolam (n = 326) or BDZ (n = 322) administration, there is no significant difference between the two groups {(mean difference = -0.03; 95% CI [-1.30, 1.25]), P = 0.97} and both are equally effective for controlling acute seizures (odds ratio = 1.06; 95% CI [0.43, 2.63]; n = 737). CONCLUSION: In children with acute seizures, IN midazolam is equally effective in aborting seizure and decreases the total time from hospital arrival and cessation of seizures, eventually leading to faster cessation of seizure as compared to IV/rectal BDZ.

Effect of valproate and add-on levetiracetam on inflammatory biomarkers in children with epilepsy.

BACKGROUND: Contemporary research indicates the role of neuroinflammation/inflammatory markers in epilepsy. In addition, comorbidities such as anxiety and poor health-related quality of life are vital concerns in clinical care of pediatric patients with epilepsy. This open-label, prospective, observational study evaluated the effect of valproate and add-on levetiracetam on serum levels of C-C motif ligand 2 (CCL2) and Interleukin-1 beta (IL-1ß) in pediatric patients with epilepsy. We also studied effect of valproate and add-on levetiracetam on anxiety and health-related quality of life (HRQoL) in specified age subgroups. METHODS: Children aged 1 to 12 years, diagnosed with epilepsy (generalized or focal seizures), treated with valproate (n = 40) and valproate with add-on levetiracetam (n = 40) were included. All patients were followed up for 16 weeks and assessed for changes in serum CCL2 and IL-1ß levels. Spence Children Anxiety Scale short version (SCAS-S) and QOLCE-16 scales were used to measure anxiety and HRQoL, respectively, in specific age groups. RESULTS: The serum CCL2 level decreased significantly (p < .001) from 327.95 ±â€¯59.07 pg/ml to 207.02 ±â€¯41.50 pg/ml in the valproate group and from 420.65 ±â€¯83.72 pg/ml to 250.06 ±â€¯46.05 pg/ml in the add-on levetiracetam group. Serum IL-1ß level did not change significantly in both groups. Spence Children Anxiety Scale short version scores were decreased and QOLCE-16 scores were increased significantly (p < .001) in both valproate and add-on levetiracetam groups. CONCLUSIONS: The results of our study suggest that valproate and levetiracetam led to decrease serum CCL2 levels without any change in serum IL-1ß levels in children with epilepsy. Anti-inflammatory property of valproate and levetiracetam might underlie their antiepileptic effect and CCL2 could be a potential marker of drug efficacy in epilepsy. Also, valproate and levetiracetam reduced anxiety and improved quality of life in children with epilepsy in the age groups evaluated.

Isolated Fetal Ascites: Etiology and Prognosis - A 10-Year Experience from a Tertiary Referral Care Center in India.

INTRODUCTION: Isolated fetal ascites is an uncommon finding, and it may be difficult to elucidate the underlying pathology. This is more so when there are limited resources to investigate the patient adequately. This study was undertaken to see the etiology of isolated fetal ascites and analyze the outcomes. MATERIALS AND METHODS: Twenty-three cases of isolated fetal ascites were retrospectively analyzed from December 2007 to June 2018. All cases were investigated with detailed ultrasound with other investigations as required. Postnatal data included gestational age at birth, mode of delivery, weight, and postnatal outcome. RESULTS: The mean age at diagnosis was 26 gestational weeks. Structural abnormalities without any underlying chromosomal or genetic cause were identified in 10/23 (43.4%) cases with the most common structural abnormality related to the gastrointestinal tract where ultrasound proved to the most useful tool. The overall good prognosis was seen in 13/23 (56.5%) cases. CONCLUSION: Appropriate perinatal care, timely referral and delivery at tertiary care setup, and timely surgical intervention are measures which can improve the outcome and survival in fetuses diagnosed with isolated fetal ascites.

Assessment of anti-CarP antibodies, disease activity and quality of life in rheumatoid arthritis patients on conventional and biological disease-modifying antirheumatic drugs.

OBJECTIVE: Good biomarkers are important to guide decisions in the clinical management of rheumatoid arthritis (RA). RA patients harbor antibodies directed against carbamylated proteins which may predict joint damage. This study investigated whether antibodies against carbamylated proteins (anti-CarP) may serve as surrogate prognostic markers. MATERIAL AND METHODS: Fifty-three patients with a diagnosis of rheumatoid arthritis according to ACR 1987 criteria were included. Blood samples were analyzed for CarP antibody levels using the ELISA method. Quality of life (QoL) was assessed by the WHO SF-36 questionnaire, and disease activity was assessed using the DAS28 calculator. Newly diagnosed patients were assessed at the first visit and at 12 weeks of treatment, while a single assessment was made for patients already on maintenance therapy. RESULTS: Out of 53 patients, 22 had titers of anti-CarP above the cut-off range and considered as positive for anti-CarP antibodies. Anti-CarP antibody serum level was significantly higher in patients with deformity of joints and with erosions in comparison to those without any destructive changes (p < 0.05). There was a weak positive correlation between anti-CarP and DAS 28 (p > 0.05). Also there was a weak negative correlation in all domains of quality of life with anti-CarP antibody titers (p > 0.05). There was no significant correlation between titers of anti-CarP antibodies and presence or absence of rheumatoid factor. CONCLUSIONS: Serum levels of anti-CarP antibodies in RA patients with joint erosions/deformities were much higher than in those without any joint damage. Anti-CarP antibodies may have good prognostic value in RA patients with erosions. Disease activity and QoL of RA patients improved during treatment, but no correlation was found between DAS 28/QoL and anti-CarP antibody serum levels.

Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression.

BACKGROUND: This study evaluated the clinical efficacy of mirtazapine and its effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) levels in patients of major-depressive disorder (MDD) with severe depression. METHODS: Patients (aged 18-60) with MDD diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥25 were included (n = 30). Mirtazapine was given in the doses of 30 mg/day. All patients were followed up for 12 weeks for the evaluation of clinical efficacy, safety along with serum BDNF and TNF-α levels. RESULTS: HAM-D score at the start of treatment was 30.1 ± 1.92, which significantly (p < 0.05) reduced to 13.47 ± 1.77 at 12 weeks of treatment. In responders, mean serum BDNF levels at the start of treatment were 2.32 ± 0.3 ng/ml, which significantly (p < 0.05) increased to 2.79 ± 0.33 ng/ml at 12 weeks of treatment and mean serum TNF-α levels at the start were 5.18 ± 0.67 pg/ml, which significantly decreased to 4.36 ± 0.72 pg/ml (p < 0.05) at 12 weeks of treatment. CONCLUSION: Our results suggest that mirtazapine is effective and well tolerated in severely depressed patients and treatment response is associated with an increase in serum BDNF and a decrease in serum TNF-α levels.

Ocular manifestations of head injury and incidence of post-traumatic ocular motor nerve involvement in cases of head injury: a clinical review.

As the eyes are in close proximity to the skull, they can get simultaneously affected in head injuries. This close association warrants careful ocular examination in all cases of head injury. This is a prospective non-randomized analytical study to evaluate various ocular manifestations in cases of head injury with special reference to ocular motor nerve involvement, correlation between pupillary changes, and survival. A total of 1,184 patients with head injury were screened for ocular manifestations. This study comprises 594 patients with ocular manifestations of head injury. All the relevant data was compiled and analyzed as per proforma. Ocular manifestations were evaluated in each patient and appropriate investigations were carried out. Patients with ocular morbidity were analyzed for age, sex, mode of injury, Glasgow Coma Score, and associated injuries in addition to ophthalmic and neurosurgical evaluations. Of the 594 patients, 81.6 % were male and 18.4 % were female, with a male-to-female ratio of 4:1. The major cause of head injury was road traffic accidents (70.37 %). The most common age group involved was, 21-40-year-olds (67.40 %). Out of 594 patients, ecchymosis was found in 51.85 %, subconjunctival hemorrhage in 44.44 %, lid edema in 41.48 %, lacerated wound in 22.59 %, pupillary involvement in 21.04 %, ptosis in 6.73 %, cranial nerve palsy in 11.62 %, orbital fractures in 10.44 %, optic nerve trauma in 4.04 %, and exposure keratitis in 4.21 %. Patients with bilaterally dilated or pinpoint fixed pupils had a 10 times higher risk of mortality than patients without pupillary involvement. Third nerve involvement was seen 2.85 times more frequently in frontal and parietal region injuries compared to other sites of injury. The involvement of the sixth nerve occurred 4.6 times more frequently in parietal region injuries compared to other sites of injury.

Optimization of foaming process for development of modified aloe polysaccharide (MAP) juice and powder using foam-mat drying.

The present study was performed to optimize the modified aloe polysaccharide (MAP) foaming process and to determine the effect of drying process parameters on the quality of obtained MAP powder. The studied process parameters were glycerol monostearate (GMS), carboxymethyl cellulose (CMC), and whipping time (WT) which was varied between 1 and 4% w/v, 0.1-0.5% w/v, and 1-5 min, respectively. The optimized values of foaming process parameters were 3.87% GMS, 0.39% CMC, and 4.89 min WT with a desirability of 0.889. The optimized foamed MAP juice was dried at different foam thicknesses (FT) (1, 3, and 5 mm) and drying temperatures (DT) (50, 60, and 70 °C) to develop MAP powder and compared with non-foamed aloe powder developed under the same drying condition. Based on functional properties, the best GMS foamed MAP powder was achieved at 50 °C DT and 1 mm FT, recording powder yield (16%), solubility (20.85%), and polysaccharide content (282 mg/L). Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01354-6.

Dextromethorphan-Induced Altered Level of Consciousness in Children: A Case Series.

BACKGROUND: Dextromethorphan, an N-methyl-d-aspartate receptor antagonist, has been used as cold and cough medication. Serious adverse events with therapeutic doses of dextromethorphan are rarely observed. Here, we report three cases of altered levels of consciousness in children with a therapeutic dose of dextromethorphan. CASE PRESENTATION: In all three cases, children developed an altered level of consciousness after taking the first dose of syrup dextromethorphan. Children were unresponsive to any verbal command and pain stimuli. Medical history revealed no pre-existing comorbidities. Other systemic, cardiovascular, abdominal, respiratory and nervous system examinations were normal. All patients were hospitalised and managed with symptomatic and supportive care. Dextromethorphan was stopped. After adequate treatment, all of them recovered satisfactorily. The causality assessment was done based on the World Health Organization Uppsala Monitoring Centre causality scale, and it was probable/likely in all three cases. CONCLUSION: In children, an altered level of consciousness could occur with therapeutic doses of dextromethorphan; hence, health care professionals should prescribe dextromethorphan with extreme caution.

Recent Advances in Polymer-Based Nanomaterials for Non-Invasive Photothermal Therapy of Arthritis.

To date, nanomaterials have been widely used for the treatment and diagnosis of rheumatoid arthritis. Amongst various nanomaterials, polymer-based nanomaterials are becoming increasingly popular in nanomedicine due to their functionalised fabrication and easy synthesis, making them biocompatible, cost-effective, biodegradable, and efficient nanocarriers for the delivery of drugs to a specific target cell. They act as photothermal reagents with high absorption in the near-infrared region that can transform near-infrared light into localised heat with fewer side effects, provide easier integration with existing therapies, and offer increased effectiveness. They have been combined with photothermal therapy to understand the chemical and physical activities behind the stimuli-responsiveness of polymer nanomaterials. In this review article, we provide detailed information regarding the recent advances in polymer nanomaterials for the non-invasive photothermal treatment of arthritis. The synergistic effect of polymer nanomaterials and photothermal therapy has enhanced the treatment and diagnosis of arthritis and reduced the side effects of drugs in the joint cavity. In addition, further novel challenges and future perspectives must be resolved to advance polymer nanomaterials for the photothermal therapy of arthritis.

Effect of milnacipran on brain­derived neurotrophic factor and oxidative stress biomarkers in patients of major depressive disorder.

Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) suggest important role of neurotrophic factors and oxidative stress. This study assessed the effect of milnacipran (a dual serotonin­noradrenaline reuptake inhibitor) on brain­derived neurotrophic factor (BDNF) and oxidative stress biomarkers i.e., malondialdehyde (MDA), glutathione­s­ transferase (GST) and glutathione reductase (GR) in patients of MDD. Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM­IV criteria, with Hamilton Depression Rating scale (HAM­D) score ≥ 14 were included in the study. Patients were given milnacipran in the doses of 50­100 mg once daily. Patients were followed up for 12 weeks. HAM­D score at the start of treatment was 17.8±1.7 which significantly reduced to 8.9±3.1 at 12 weeks of treatment. In responders, the plasma BDNF levels increased significantly at 12 weeks post treatment. There was no significant change in the pre­ and post­treatment values of oxidative stress parameters (MDA, GST and GR) after 12 week treatment. Milnacipran is effective and well tolerated in MDD patients, and its therapeutic response is associated with an increase in plasma BDNF levels. However, milnacipran did not affect oxidative stress biomarkers.