Clinical characteristics of bipolar disorder in very young children

BACKGROUND: Clinical information about bipolar disorder (BPD) in preschool-age (3-7 years old) children is extremely limited. This study examined clinical presentations, applicability of the DSM-IV diagnostic criteria, comorbidity, recovery and relapse rates, as well as some treatment strategies used in the management of BPD in preschoolers. METHODS: The charts of 26 outpatient children, ages 3-7, refereed to a child psychiatry outpatient clinic with mood and behavioral symptoms, were retrospectively reviewed. RESULTS: The majority of the patients were referred with the tentative diagnosis of ADHD but the most common diagnoses made by child and adolescent psychiatrists at the time of initial evaluation were BPD NOS (61.5%), followed by BPD I (26.9%), and mood disorder NOS (23.1%). Thirty-eight percent of the patients had one or more comorbid diagnoses. The most common presenting symptoms were irritability (84.6%) and aggression (88.5%). The most widely prescribed class of medications after diagnosis in the clinic was atypical antipsychotics and mood stabilizers. Twenty-six percent of the patients were treated with a combination of atypical antipsychotics and mood stabilizers. LIMITATIONS: Retrospective design; small sample size; lack of a comparison group. CONCLUSIONS: The course of BPD with onset in preschool years is complicated with high recovery and relapse rates. The questions of development of age-appropriate diagnostic criteria, long-term prognosis and treatment strategies used in this population require further intensive investigation.     

Sustained Simultaneous Delivery of Metronidazole and Doxycycline From Polycaprolactone Matrices Designed for Intravaginal Treatment of Pelvic Inflammatory Disease

Poly(?-caprolactone) (PCL) intravaginal matrices were produced for local delivery of a combination of antibacterials, by rapidly cooling a mixture of drug powders dispersed in PCL solution. Matrices loaded with different combinations of metronidazole (10%, 15%, and 20% w/w) and doxycycline (10% w/w) were evaluated in vitro for release behavior and antibacterial activity. Rapid “burst release” of 8%-15% of the doxycycline content and 31%-37% of the metronidazole content occurred within 24 h when matrices were immersed in simulated vaginal fluid at 37°C. The remaining drug was extracted gradually over 14 days to a maximum of 65%-73% for doxycycline and 62%-71% for metronidazole. High levels of antibacterial activity up to 89%-91% against Gardnerella vaginalis and 84%-92% against Neisseria gonorrhoeae were recorded in vitro for release media collected on day 14, compared to “nonformulated” metronidazole and doxycycline solutions. Based on the in vitro data, the minimum levels of doxycycline and metronidazole released from PCL matrices in the form of intravaginal rings into vaginal fluid in vivo were predicted to exceed the minimum inhibitory concentrations for N. gonorrhea (reported range 0.5-4.0 μg/mL) and G. vaginalis (reported range 2-12.8 μg/mL) respectively, which are 2 of the major causative agents for pelvic inflammatory disease.     

Synthesis,molecular docking,and pharmacological evaluation of N‐(2‐(3,5‐dimethoxyphenyl)benzoxazole‐5‐yl)benzamide derivatives as selective COX‐2 inhibitors and anti‐inflammatory agents

A series of N‐(2‐(3,5‐dimethoxyphenyl)benzoxazole‐5‐yl)benzamide derivatives ( 3am ) was synthesized and evaluated for their in vitro inhibitory activity against COX‐1 and COX‐2. The compounds with considerable in vitro activity (IC₅₀ < 1 μM) were evaluated in vivo for their anti‐inflammatory potential by the carrageenan‐induced rat paw edema method. Out of 13 newly synthesized compounds, 3a , 3b , 3d , 3g , 3j , and 3k were found to be the most potent COX‐2 inhibitors in the in vitro enzymatic assay, with IC₅₀ values in the range of 0.06–0.71 μM. The in vivo anti‐inflammatory activity of these six compounds ( 3a , 3b , 3d , 3g , 3j , and 3k ) was assessed by the carrageenan‐induced rat paw edema method. Compounds 3d (84.09%), 3g (79.54%), and 3a (70.45%) demonstrated significant anti‐inflammatory activity compared to the standard drug ibuprofen (65.90%) and were also found to be safer than ibuprofen, by ulcerogenic studies. A docking study was done using the crystal structure of human COX‐2, to understand the binding mechanism of these inhibitors to the active site of COX‐2.

     

Validation of the eleven-point pain scale in the measurement of migraine headache pain

The four-point pain scale (none, mild, moderate, severe) and the 11-point pain scale (0 = no pain, 10 = pain as bad as it could be) have been used in migraine studies to assess treatment efficacy. The primary objective of this study was to investigate the validity and responsiveness of the 11-point pain scale using the four-point pain scale as a benchmark. Using data from 95 migraine patients recruited from headache clinics, this study found that 11-point pain scale scores were highly correlated with four-point pain scores. The correlations between the pain scales were significantly higher than the correlations with quality of life measures such as functional ability and emotional feelings. The 11-point pain scale was 55% more sensitive than the four-point pain scale in detecting clinically important differences. The strong linear relationship between the two pain scales allowed researchers to transform four-point pain scores to 11-point pain scores using regression weights.     

Novel heteroleptic complexes of titanium(IV) derived from 2-hydroxyacetophenone: synthesis, characterization, antibacterial and molecular docking studies

A few new and versatile complexes of titanium(IV) derived from 2-hydroxyacetophenone of the types {[(Ap)Ti(OPr ⁱ )_2?n (L₂) _n ] (2a, 2e and 2f)}, {[(Ap)Ti(L₁OR)(L₂)] (2b–2d, 2g–2i)} have been synthesized by the reaction of the precursor [(Ap)Ti(OPr ⁱ )₂] with different 2-heteroaryl methyl ketone oximes and alkoxyalkanols in various molar ratios in refluxing toluene yielded mono nuclear heteroleptic derivatives, {where, n = 1–2, HAp = 2-hydroxyacetophenone, Pr ⁱ  = isopropyl, L₁ = O–CH₂–CH₂?, R = CH₃, C₂H₅, C₄H₉ and HL₂=HONC(Me)py-2, HONC(Me)fu-2}. All these newly synthesized complexes were characterized by elemental analysis, mass, UV, FT-IR and NMR (¹H, ¹³C) spectral studies. The mass spectra of the newly synthesized molecules indicate their monomeric state. Spectral studies suggest the bonding between metal and ligands in a tetra coordinated fashion. Thermogravimetric analyses indicate the multistep decomposition of complexes resulting TiO₂ as the end product at 600 °C. Antibacterial activities of these complexes were also exercised. Complex 2e is equipotent to the standard drug against Pseudomonas aeruginosa and Escherichia coli. A keen molecular docking study revealed lesser docking scores of some of these complexes than that of the standard drug gentamicin.     

Acute and subchronic dermal toxicity of Vitex negundo essential oil

Vitex negundo is a common herb in different herbal formulation. The potential acute and sub-chronic dermal toxicities were evaluated as per OECD (Organization for Economic Cooperation and Development) guidelines 402 and 411, respectively. Both sexes of Wistar rats were exposed to Vitex negundo oil of 2000?mg/kg body weight for acute dermal toxicity, whereas in the dermal sub-chronic toxicity study, rats were exposed to Vitex negundo oil 250, 500 and 1000?mg/kg body weight, respectively, for five times a week for 90?d. In acute and sub-chronic toxicity studies, all animals were normal without any behavioral, serum biochemistry, hematology, necroscopical and histopathological changes. The no observed effect level (NOEL) and no observed adverse effect level (NOAEL) of Vitex negundo oil were 250 and 1000?mg/kg/day, respectively. Vitex negundo oil is under the category 5 (Unclassified) according to the Globally Harmonized System, with an LD₅₀ value of over 2000?mg/kg.     

Improvement of Sleep Disturbance and Insomnia Following Parathyroidectomy for Primary Hyperparathyroidism

Background

The aim of the present study was to investigate the incidence of sleep disturbance and insomnia in patients with primary hyperparathyroidism (PHPT), and to evaluate the effect of parathyroidectomy.

Methods

A questionnaire was prospectively administered to adult patients with PHPT who underwent curative parathyroidectomy over an 11-month period. The questionnaire, administered preoperatively and 6 months postoperatively, included the Insomnia Severity Index (ISI) and eight additional questions regarding sleep pattern. Total ISI scores range from 0 to 28, with >7 signifying sleep difficulties and scores >14 indicating clinical insomnia.

Results

Of 197 eligible patients undergoing parathyroidectomy for PHPT, 115 (58.3 %) completed the preoperative and postoperative questionnaires. The mean age was 60.0 ± 1.2 years and 80.0 % were women. Preoperatively, 72 patients (62.6 %) had sleep difficulties, and 29 patients (25.2 %) met the criteria for clinical insomnia. Clinicopathologic variables were not predictive of clinical insomnia. There was a significant reduction in mean ISI score after parathyroidectomy (10.3 ± 0.6 vs 6.2 ± 0.5, p < 0.0001). Postoperatively, 79 patients (68.7 %) had an improved ISI score. Of the 29 patients with preoperative clinical insomnia, 21 (72.4 %) had resolution after parathyroidectomy. Preoperative insomnia patients had an increase in total hours slept after parathyroidectomy (5.4 ± 0.3 vs 6.1 ± 0.3 h, p = 0.02), whereas both insomnia patients and non-insomnia patients had a decrease in the number of awakenings (3.7 ± 0.4 vs 1.9 ± 0.2 times, p = 0.0001).

Conclusions

Sleep disturbances and insomnia are common in patients with PHPT, and the majority of patients will improve after curative parathyroidectomy.