Sleep parameters improvement in PTSD soldiers after symptoms remission.

Eye movement desensitization and reprocessing (EMDR) is a psychotherapy for the treatment of posttraumatic stress disorder (PTSD). It is still unclear whether symptoms remission through EMDR therapy is associated with a beneficial effect on one of the PTSD symptoms, sleep disturbance. Our objective was therefore to study sleep parameters before and after symptom remission in soldiers with PTSD. The control group consisted of 20 healthy active duty military men who slept in a sleep lab with standard polysomnography (PSG) on two sessions separated by one month. The patient group consisted of 17 active duty military with PTSD who underwent EMDR therapy. PSG-recorded sleep was assessed 1 week before the EMDR therapy began and 1 week after PTSD remission. We found that the increased REMs density after remission was positively correlated with a greater decrease of symptoms. Also, the number of EMDR sessions required to reach remission was correlated with intra-sleep awakenings before treatment. These results confirm the improvement of some sleep parameters in PTSD after symptoms remission in a soldier's population and provide a possible predictor of treatment success. Further experiments will be required to establish whether this effect is specific to the EMDR therapy.

Smell training in prolonged COVID-19 post-infectious olfactory dysfunction: A case report

Objective@#To report the case of a woman who underwent smell training for post-infectious olfactory dysfunction presumably from COVID-19. @*Methods@#Design: Case Report. Setting: Tertiary Private Training Hospital. Patient: One. @*Result@#A 41-year-old woman who developed olfactory dysfunction attributed to COVID-19 underwent smell training. At baseline, her responses were mostly “no smell,” and those reported as “can smell a bit” were rated as distorted. After three months, she could now smell items that she previously could not smell, but these smells were still distorted. At the time of this writing, she was on her 4th month of smell training. @*Conclusion@#Although we cannot rule out spontaneous resolution of anosmia in our patient, we would like to think that smell training contributed to her recovery of smell.

Incorporation of fragmented visuo-olfactory episodic memory into dreams and its association with memory performance.

The question of a possible link between dream content and memory consolidation remains open. After a comprehensive review of the literature, we present novel findings from an experiment testing whether the incorporation of recently learned stimuli into dream reports is associated with improved post-sleep memory performance. Thirty-two high dream recallers freely explored new visuo-olfactory episodes for 3 consecutive days. During the nights following each non-explicit encoding, participants wore a wrist actimeter, and woke up at 5am and their usual waking time to record their dreams (intensity of all oneiric sensory perception was assessed using scales). A total of 120 dreams were reported and elements related to the encoding phase were identified in 37 of them, either learning-related (mainly visual- and rarely olfactory-related elements), or experiment-related (lab- or experimenters-related elements). On the 4th day, we found that participants with learning-related (n = 16) and participants with learning-related and/or experiment-related dreams (n = 21) had similar odor recognition and odor-evoked episodic memory with the other participants. However, they had significantly better visuo-spatial memory of the episodes in comparison to the other participants. Our results support the hypothesis that the learning phase is loosely incorporated into dreams and that this incorporation is associated with sleep related memory consolidation.

Workplace-based assessment of family medicine competencies using "field note tool" - A pilot study.

BACKGROUND: Department of Family Medicine in a medical college in South India introduced "field note" (FN) as a tool for Work-Place Based Assessment in postgraduate training. FN collects "open-ended" feedback from both resident and faculty and helps them to arrive at an action plan. This study describes our experience of implementing FN and perceptions of learners and faculty. METHODS: While precepting the residents in Family Medicine service areas, faculty documented their observations of the resident's clinical work using FN and provided an action plan. Faculty and residents described their experience and provided feedback. Focus group discussions were conducted for faculty and residents. Data were coded and grouped into themes. RESULTS: Four residents and seven faculties participated in the study during 12 weeks period using 17 consultations. Clinical expert (13/17) and communicator (6/17) are the most commonly assessed competencies followed by professionalism (2/17) and collaborator (2/17). Faculty and residents agreed that "FN" was a useful tool and it helped the faculty to give feedback and guide the learner. Residents and faculty arrived at an action plan in 70% of the consultations. Three of four residents perceived the change in their behaviour positively after the use of FN. Both resident and faculty found the rating of the learner using Dreyfus scale as a barrier. CONCLUSION: FN could be one of the important tools in our "Toolbox of Assessment Methods" for family medicine specialty. There is a need for sensitizing the learners to feedback process and training the faculty in assessment and feedback.

Initial otoacoustic emission hearing screening results in newborns with patent ear canals, vernix caseosa and collapsed ear canals

@#<p style="text-align: justify;"><strong>OBJECTIVES: </strong>This study determined the initial otoacoustic (OAE) hearing screening results of newborns with collapsed ear canals and vernix caseosa in the ear canal and compared these to ears that were patent.<br /><strong>METHODS:</strong> Two hundred term newborns (400 ears) with normal APGAR scores, birth weight, maternal and gestational history, who were born between August 2013 to October 2013 and who had OAE hearing screening test done by trained midwives were included in this study. All of them underwent otoscopy after the OAE hearing screening test was done to determine patency of the ear canal and presence of vernix caseosa. The examining physician was blinded to the OAE results. Comparison between the OAE results and the otoscopic findings were done.<br /><strong>RESULTS:</strong> Four hundred ears were included in the study. Two hundred and fifty one ears (62.8%) had vernix caseosa and 42 ears (10.5%) had collapsed ear canal. The overall initial OAE hearing screening test pass rate of the newborns tested was 69.5%. The initial OAE hearing screening test pass rate of newborns those with ear canal vernix caseosa or collapsed ear canal, were 72.1% and 47.6%, respectively. Patent ears were found in 107 (26.7%) with a pass rate of 71.9%.<br /><strong>CONCLUSION:</strong>The pass rates of ears with vernix caseosa and collapsed ear canal were 72.1% and 47.6%, respectively. There was no significant difference between the OAE hearing screening test pass rates of ears with patent canal and ears that were collapsed and/ or had vernix caseosa. However, there was a statistically significant difference in pass rates between patent ear canals and collapsed ear canal</p>

PARP inhibition attenuates neuroinflammation and oxidative stress in chronic constriction injury induced peripheral neuropathy.

AIM: Peripheral nerve degeneration after nerve injury is accompanied with oxidative stress that may activate poly ADP-ribose polymerase (PARP, DNA repair enzyme). PARP overactivation amplifies the neuronal damage either due to energy crisis or through inflammatory process by facilitating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Hence investigated the role of PARP inhibitors, 3-Aminobenzamide (3-AB) and 1,5-isoquinolinediol (ISO) in the attenuation of chronic constriction injury (CCI) induced peripheral neuropathy in rats. METHODS: 3-AB and ISO (at doses 30 and 3mg/kg i.p., respectively) were tested in rats subjected to standard tests for evaluating hyperalgesia and allodynia. Sciatic functional index (SFI) was assessed by performing walking track analysis. Oxidative stress and inflammation induced biochemical alterations were estimated after 14 days in sciatic nerve and lumbar spinal cord. Molecular changes were explored by immunohistochemistry and DNA fragmentation by TUNEL assay. KEY FINDINGS: Treatment significantly improved sensorimotor responses (p<0.001), SFI (p<0.001) and foot posture. PARP inhibition significantly (p<0.01 and p<0.001) reduced the elevated levels of nitrite, inflammatory markers and also normalized the depleted NAD(total) levels. The protein expression of poly (ADP-ribose) (PAR), NF-κB, cyclooxygenase-2 (COX-2) and nitrotyrosine were significantly (p<0.01 and p<0.001) decreased in both sciatic nerve and lumbar spinal cord, evident through immunohistochemistry. SIGNIFICANCE: Present study outcomes fortify the pathological role of PARP overactivation in CCI induced neuropathy and PARP inhibition ameliorated oxidative stress and neuroinflammation associated with CCI induced nerve injury. Therefore, the current study suggests the PARP inhibitors can further be evaluated for designing futuristic strategies for the management of trauma induced neuropathy.

Microalbuminuria - A better marker in hypertensive disorders of pregnancy.

To assess the role of microalbuminuria in pre-eclampsia (PE) as a diagnostic marker, we studied 40 PE cases and 40 normotensive controls at 24 ± 4 weeks of gestation in women 20-35 years of age. The patients with PE had significant microalbuminuria in comparison with the controls, in addition to deranged renal function tests. The receiver operating characteristic curve showed that microalbuminuria had the highest sensitivity (100%) and good specificity (77.6%). Microalbuminuria had the highest area under the curve (0.869) for both diagnosis of PE and renal function assessment. Microalbuminuria also had a good correlation with systolic blood pressure in the cases with mild grades of renal dysfunction. Microalbuminuria is a specific marker in PE and it also helps to assess the renal function status. Therefore, microalbuminuria may be used in the early diagnosis and management of PE patients in order to reduce the immediate and long-term complications.

Do premenopausal hypothyroid women on levothyroxine therapy need bone status monitoring?

BACKGROUND: Suppressive doses of levothyroxine therapy are reported to reduce bone mineral density (BMD) in women. Data on bone changes in premenopausal hypothyroid women with replacement therapy are limited. Hence, this study was undertaken to evaluate bone changes in this group using bone markers and BMD. MATERIALS AND METHODS: A hospital-based case-control study including 75 premenopausal women aged 30-45 years was conducted. The subjects were categorized based on their thyroid function and history into three groups of 25 euthyroid, 25 newly diagnosed hypothyroid, and 25 hypothyroid women on 100-200 µg of levothyroxine for a minimum of 5 years. The bone changes were evaluated and compared among the groups biochemically by estimating their plasma osteocalcin and serum calcium and phosphorus and radiologically by measuring their BMD by quantitative ultrasonography. Statistical analysis was conducted by using analysis of variance, Tukey's test, and Pearson's correlation using IBM SPSS Statistics 20. RESULTS: Levels of plasma osteocalcin, serum calcium, and serum phosphorus in patients on long-term levothyroxine therapy were significantly higher than those in newly diagnosed hypothyroid women and in the euthyroid group. BMD showed definite features of osteopenia (T-score: -2.26 ± 0.5) among the women in the treatment group, while it was well within the normal range in the newly diagnosed and euthyroid women. A significant correlation was found between the osteocalcin levels and T-score. CONCLUSION: Hypothyroid women on long-term levothyroxine therapy showed signs of increased bone turnover and increased resorptive changes, though not frank osteoporosis. Hence, it may be important to evaluate the bone status of patients on levothyroxine for >5 years.

Detection of glutaric acidemia type 1 in infants through tandem mass spectrometry.

Glutaric acidemia type 1 (GA1) is a rare inherited metabolic disorder which goes underdiagnosed due to its latency period and subtle presentation. A pilot clinical study was conducted to assess the usefulness, specificity and sensitivity of the tandem mass (MS/MS) spectrometer, specifically the Abbott (AB) Sciex 3200, in the screening for GA1 using dried blood spots. A total of 17,100 specimens, comprising pediatric patients and healthy newborns, were screened from June 2012 to June 2014. A selection criterion was applied to increase the range of samples tested. 14 of the total specimens tested presumptive positive for GA1, of whom all were symptomatic. The diagnosis was confirmed in 4 of the 14 cases and they were started on treatment. 4 cases expired before confirmation. The remaining cases were empirically started on treatment. Most of the patients responded favorably to the dietary management. One important observation was that the older symptomatic children diagnosed with GA1 had poorer outcomes in terms of recovery of delayed milestones and mental deterioration, further emphasizing the need for early diagnosis of organic acidemias along with the other biochemical defects. Tandem mass spectrometry was found to be more than 93.33% sensitive and more than 99.42% specific. The screening test proved to be very simple and economical.

Role of Family Medicine Education in India's Step Toward Universal Health Coverage.

India's commitment to universal health coverage has grown stronger with the submission of High Level Expert Group report by the Planning Commission in 2012. With this report comes the commitment to increase the primary health-care workforce to meet the population needs. However, the focus should not be just to increase the number of health workers, but to produce better health workers. Doctors, nurses and community health workers trained in primary and secondary health-care facilities can make a significant contribution in responding to the needs of the local community. The role of family medicine education is worth exploring in this context to equip the primary care health workers with the competencies of providing person-centered, comprehensive and continuous care.

Utility of C-terminal Telopeptide in Evaluating Levothyroxine Replacement Therapy-Induced Bone Loss.

BACKGROUND: Levothyroxine (LT4) therapy has shown to have effects on bone metabolism though its deleterious effect on bone remodeling is debatable. This study was aimed at assessing the diagnostic utility of the bone remodeling marker C-terminal telopeptide (CTx) in detecting early bone loss. MATERIALS AND METHODS: In this case-control study, 84 premenopausal women of 30-45 years of age were selected. Out of them, 28 were recently diagnosed of hypothyroidism (not on LT4), 28 were on LT4 replacement therapy (100-200 µg/day) for more than five years, and 28 had euthyroid. Plasma CTx levels were estimated. Bone mineral density (BMD) was measured by quantitative ultrasound (QUS) method. Pearson's coefficient of correlation and ANOVA were used for statistical analysis. RESULTS: CTx was most elevated in LT4-treated group (0.497 ± 0.209 ng/mL). It showed a significant negative correlation with T-score and Z-score of BMD values. In the treatment group of more than 150 µg/day, CTx showed significantly negative correlation with TSH (r = -0.462, P = 0.047). CONCLUSION: LT4 therapy induces bone loss in hypothyroid patients. CTx levels can measure such bone loss along with BMD. Regular monitoring of CTx with adjustment in LT4 doses may help delay osteoporosis induced by prolonged LT4 replacement therapy.

Influence of iron deficiency anemia on hemoglobin A1c levels in diabetic individuals with controlled plasma glucose levels.

INTRODUCTION: Hemoglobin A1C (HbA1c) reflects patient's glycemic status over the previous 3 months. Previous studies have reported that iron deficiency may elevate A1C concentrations, independent of glycemia. This study is aimed to analyze the effect of iron deficiency anemia on HbA1c levels in diabetic population having plasma glucose levels in control. METHODS: Totally, 120 diabetic, iron-deficient anemic individuals (70 females and 50 males) having controlled plasma glucose levels with same number of iron-sufficient non-anemic individuals were streamlined for the study. Their data of HbA1c (Bio-Rad D-10 HPLC analyzer), ferritin (cobas e411 ECLIA hormone analyzer), fasting plasma glucose (FPG, Roche Hitachi P800/917 chemistry analyzer), hemoglobin (Beckman Coulter LH780), peripheral smear examination, red cell indices, and medical history were recorded. Statistical analysis was carried out by student's t-test, Chi-square test, and Pearson's coefficient of regression. RESULTS: We found elevated HbA1c (6.8 ± 1.4%) in iron-deficient individuals as compared to controls, and elevation was more in women (7.02 ± 1.58%). On further classification on the basis of FPG levels, A1C was elevated more in group having fasting glucose levels between 100-126 mg/dl (7.33 ± 1.55%) compared to the those with normal plasma glucose levels (<100 mg/dl). No significant correlation was found between HbA1c and ferritin and hemoglobin. CONCLUSION: This study found a positive correlation between iron deficiency anemia and increased A1C levels, especially in the controlled diabetic women and individuals having FPG between 100-126 mg/dl. Hence, before altering the treatment regimen for diabetic patient, presence of iron deficiency anemia should be considered.

Critical attributes of transdermal drug delivery system (TDDS)--a generic product development review.

Bioequivalence testing of transdermal drug delivery systems (TDDS) has always been a subject of high concern for generic companies due to the formulation complexity and the fact that they are subtle to even minor manufacturing differences and hence should be clearly qualified in terms of quality, safety and efficacy. In recent times bioequivalence testing of transdermal patches has gained a global attention and many regulatory authorities worldwide have issued recommendations to set specific framework for demonstrating equivalence between two products. These current regulatory procedures demand a complete characterization of the generic formulation in terms of its physicochemical sameness, pharmacokinetics disposition, residual content and/or skin irritation/sensitization testing with respect to the reference formulation. This paper intends to highlight critical in vitro tests in assessing the therapeutic equivalence of products and also outlines their valuable applications in generic product success. Understanding these critical in vitro parameters can probably help to decode the complex bioequivalence outcomes, directing the generic companies to optimize the formulation design in reduced time intervals. It is difficult to summarize a common platform which covers all possible transdermal products; hence few case studies based on this approach has been presented in this review.

In vitro and in vivo equivalence testing of nanoparticulate intravenous formulations.

The topic of bioequivalence evaluation of nanoparticulate intravenous formulations is one that has been intensely debated in recent times since the release of the specific recommendations by many regulatory authorities worldwide. Product specific bioequivalence guidelines for many of the nanoparticulate systems where therapeutic molecules are directly coupled (human albumin bound paclitaxel nanosuspension), functionalized (iron- carbohydrate preparations) or entrapped/coated to a carrier (doxorubicin liposomal formulations), have been approved by the drug regulatory agencies. These current regulatory procedures include complete characterization of the generic formulation in terms of its physicochemical characteristics, pharmacokinetics disposition and/or non clinical testing with respect to the reference formulation. The concept of in vitro equivalency is emerging as a valuable tool in these guidances as generic product differing in in vitro parameters can result in a different biopharmaceutical profile with respect to pharmacokinetics and biodistribution. Furthermore, in case of systems with entrapped drug, classical pharmacokinetic parameters alone may only ensure the equivalent clearance of test and reference product from systemic circulation but may fail to detect the extent to which the nanoparticles are taken up by different target organs and, consequently, the safety and efficacy effects. Hence, additional tissue distribution study in preclinical study models has reflected in recent guidances. Understanding and interpretation of these regulatory requirements thus presents most critical component of a generic product development cycle. This article reviews these current regulatory procedures with special emphasis on in vitro population bioequivalence (POP BE) and preclinical testing of generic formulations.

International classification of primary care: an Indian experience.

BACKGROUND: India is in the process of transition to universal health coverage for Indian citizens. The focus is to strengthen the primary and secondary level services. Coupled with this national scenario, the development of Family medicine as a distinct discipline is in a crucial stage. There is a nation-wide urge to build family medicine training units and service centers across the country to fulfill the unmet health needs of the population. OBJECTIVES: This study aimed to bring out reasons for encounter (RFE) and morbidity pattern of patients seen in a family physician run urban health center in South India. METHODS: The study was conducted in an urban health center of a tertiary care hospital. Clinicians entered the data using International Classification of Primary Care (ICPC) codes. Data included were demographics, 3 RFE, 3 diagnoses, 3 outcomes of care that include prescriptions, investigations, procedures, and referrals made. RESULTS: During 47,590 patient encounters, 59,647 RFE, 62,283 diagnoses and 68269 outcomes of care were recorded. The majority of RFEs and diagnoses are in the following ICPC chapters: Endocrinology (38.6%), cardiovascular (35.91%), respiratory (20.26%), digestive (7.68% and musculo-skeletal (6.8%). The most frequent outcome of care was prescriptions, followed by counseling and nebulization. CONCLUSION: This study is the first to report on the RFE in India. This study demonstrated the breadth of clinical conditions seen by family physicians across all ages and in both genders. This study attempts to highlight the need for family physician based services as a training ground for trainees.

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

Elevation of HbA1C in Non-diabetic Hypothyroid Individuals: Is Anaemia the Connecting Link? -A Preliminary Study.

AIM: Studies have shown elevated HbA1C in non-diabetic hypothyroid patients. Hypothyroid patients often show anaemia as an associated feature which is an another condition showing falsely elevated A1C. Hence this study is aimed to investigate whether elevated A1C in hypothyroidism can be attributed to anaemia. MATERIAL AND METHODS: HbA1C levels of 120 non-diabetic hypothyroid patients (30 microcytic hypochromic anaemia, 30 normocytic normochromic anaemia and 60 non anemic patients) with 120 age, sex, plasma glucose levels and anaemia status matched controls were assessed. Anaemia status was determined by ferritin, Haemoglobin, red cell indices and peripheral smear. Glycemic status was determined by fasting Plasma glucose. RESULTS: HbA1C levels in hypothyroid patients with hypochromic microcytic anaemia and normocytic normochromic anaemia were 6.82 ± 0.71% & 6.32 ± 0.75% against 6.43 ± 0.43% & 5.87 ± 0.46 % of euthyroid anaemia matched controls respectively. While hypothyroid non anemic patients showed A1C levels of 5.91 ± 0.31% against 5.46 ± 0.62% of euthyroid non anemic controls. Hypothyroid Patients with anaemia had a significant odds ratio 3.16 (95% CI 1.426-7.016) for HbA1C > 6.5. DISCUSSION AND CONCLUSION: Non-diabetic hypothyroid individuals with anaemia shows elevate A1C levels in prediabetes range. Hence care should be excercised while using HbA1C as a diagnostic tool for diabetes in such patients.

Human synovial lubricin expresses sialyl Lewis x determinant and has L-selectin ligand activity.

Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Galß1-3(GlcNAcß1-6)GalNAcα1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation.

Not all lubricin isoforms are substituted with a glycosaminoglycan chain.

Lubricin, also referred to as superficial zone protein, has been reported to be a proteoglycan. However, the structure of its glycosaminoglycan chain has not been well characterized, and this study was undertaken to investigate the structure of the glycosaminoglycan chain that decorated lubricin in human synovial fluid to provide insight into its biological role. Lubricin was detected as a major band at approximately 360 kDa which co-migrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a chondroitin sulfate (CS)-containing proteoglycan that was detected by both monoclonal antibodies (MAb) 2-B-6 and MAb 3-B-3 after chondroitinase ABC treatment and keratan sulfate (KS) that was detected by MAb 5-D-4. Further analysis of lubricin-containing fractions that eluted from an anion exchange column indicated that the major population of lubricin could be separated from the CS and KS stubs which indicated that this fraction of lubricin was not decorated with glycosaminoglycan chain and was the glycoprotein form of lubricin. Lubricin present in fractions that also contained CS was found to be decorated with CS structures which were reactive with MAb 3-B-3 after chondroitinase ABC digestion using a sandwich enzyme-linked immunosorbent assay approach. Aggrecan was not found to form complexes with lubricin in synovial fluid which confirmed that the MAb 3-B-3 CS and MAb 5-D-4 KS structures decorated lubricin. These data demonstrate that lubricin present in human synovial fluid was a heterogeneous population with both glycoprotein and proteoglycan forms.