Distribution of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant alleles in Plasmodium vivax isolates from Thailand

The analysis of prevalence and distribution of pvdhfr and pvdhps mutations were performed in 169 samples collected from patients with Plasmodium vivax infection who attended the malaria clinics in the provinces along the three international borders of Thailand (Thai-Myanmar, Thai-Cambodian, and Thai-Malaysian borders). SNP-haplotypes of the pvdhfr at amino acid positions 13, 33, 57, 58, 61, 117, and 173 and of the pvdhps at positions 383 and 553 were examined by nested PCR-RFLP. Significant differences in the prevalence and distribution of pvdhfr and pvdhps combination alleles were observed in P. vivax isolates collected from all the three border areas. The most prevalent combination alleles were triple mutant pvdhfr 57L/58R/117T alleles/double wild-type pvdhps alleles (n = 18), double mutant pvdhfr 58R/117N alleles/double wild-type pvdhps alleles (n = 10), and triple mutant pvdhfr 58R/61M/117N alleles/double wild-type pvdhps alleles (n = 52) or with single mutant pvdhps 383G allele (n = 28), respectively. These information on prevalence and patterns of pvdhfr and pvdhps polymorphisms obtained from the present study suggest the presence of SP pressure on P. vivax isolates in Thailand which could be linked to the introduction of malaria from neighboring countries. Results did not support the application of SP for P. vivax control program in Thailand as well as the neighboring countries.     

Prevalence and Risk Assessment of Cervical Cancer Screening by Papanicolaou Smear and Visual Inspection with Acetic acid of Pregnant Women at a Thai Provincial Hospital

Background Cervical cancer is the second most common in Thailand, but the mortality rate may be rising yearly. It is a cancer that can be prevented by early screening for precancerous lesions, several methods being available. Objective To identify the prevalence of abnormal Papanicolaou (Pap) smears and lesions with visual inspection with acetic acid (VIA) in pregnant women and assess risk factors for this group. Materials and Methods This prospective study was performed at Prapokklao Hospital, Thailand during April-July 2016. All pregnant women of gestational age between 12-36 weeks who attended antenatal clinic were recruited. All participants were screened for cervical cancer by Pap smear and VIA. If results of one or both were abnormal, colposcopic examination was evaluated by gynecologic oncologist. Results A total of 414 pregnant women were recruited. Prevalence of abnormal Pap smear and VIA were 6.0 and 6.7 percent, respectively. The most common abnormal Pap smear was low grade intraepithelial lesion (LSIL, 44%). Factor associated with abnormal Pap smear in pregnant women were low BMI, multiple partners and government officer. In pregnancy, Pap smear had higher sensitivity and specificity than VIA for detection of precancerous cervical lesion. Patients with young coitarche or more than 25 years of active sexual activity were high risk groups. Conclusions Prevalence of abnormal Pap smear and VIA in pregnant women was 6.0 and 6.7 percent, respectively. Factors associated with abnormal Pap smear were coitarche, years of sexual activity, low BMI, multiple partners and government officer.     

The factors associated with successful early enteral feeding in gastroschisis

Background

Gastroschisis is the most common congenital abdominal wall defect. Due to the exposure of midgut to amniotic fluid, the recovery of bowel function is often delayed. This study aimed to identify the factors associated with the successful early enteral feeding in gastroschisis and to develop further guidelines of treatment.

Methods

A retrospective cohort study of gastroschisis babies from January 2006 to December 2015 was done. Exclusion criteria were incomplete data and death. Successful early enteral feeding was defined when full feeding was achieved within 21 days of life.

Results

One hundred and five gastroschisis patients were divided into a successful early-feeding group (n?=?56, 53%) and a non-successful early-feeding group (n?=?49, 46%). In multivariable analysis, significant factors for successful feeding clustered by primary treatment were female (RR?=?1.38, P value <?0.001), gestational age >?36 weeks (RR?=?1.23, P value <?0.001), age at surgery less than 10 h (RR?=?1.15, P value <?0.001), postoperative extubation time <?4 days (RR?=?1.39, P value <?0.001), and age when feeding started less than 10 days (RR?=?35.69, P value?<?0.001).

Conclusion

Several factors were found to be associated with successful early enteral feeding. The modifiable factors found in this study were surgery within 10 h, early postoperative extubation within 4 days, and feeding started before 10 days of life. These will guide the management of gastroschisis to achieve successful early enteral feeding.

     

Hepatocellular carcinoma screening and surveillance in 2293 chronic hepatitis B patients in an endemic area

AIM To determine the role of screening and surveillance of hepatocellular carcinoma(HCC) in treatment-na?ve chronic hepatitis B(CHB) patients. METHODS We recruited 2293 CHB patients(both males and females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography(AUS) and serum alpha-fetoprotein(AFP) assay every 6 mo. The diagnosis,staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis. The sensitivity and specificity were calculated on a per-patient basis.RESULTS Among 2293 treatment-na?ve CHB patients,seven cases had HCC at initial screening,giving a prevalence rate of 305 per 100000 persons; 3.3% were diagnosed with liver cirrhosis,all of which were Child-Pugh class A. With a median follow-up time of 42(range,3-48) mo,10 additional cases were diagnosed with HCC,resulting in an incidence rate of 143 per 100000 persons per year. This burden was as high as that reported in other studies from East Asian countries. All HCC patients were aged ≥ 40 years. Most were at an early stage(Stage 0,A or B); 14/17 cases were successfully treated with surgical resection or radiofrequency ablation,with a high 3-year survival rate of 90%. Hemangioma was the most common focal liver lesion in CHB patients detected by AUS; the main causes of AFP elevation at the initial screening were cirrhosis,increased alanine aminotransferase level and HCC. AUS detected 16/17 HCC cases whereas AFP levels ≥ 20 mg/L at diagnosis were observed in only 7/17 patients,most with a tumor size 5 cm. For HCC screening and surveillance,AUS had a sensitivity and specificity of 94% and 82%,respectively,whereas the sensitivity and specificity of AFP at a cut-off value of ≥ 20 mg/L were 41% and 98%,respectively. Combined use of AUS and AFP assay did not improve effectiveness. CONCLUSION Implementation of active screening and surveillance using AUS to detect early-stage HCC in na?ve CHB patients aged ≥ 40 years in an endemic area is of benefit.     

Bilateral sudden sensorineural hearing loss as a presentation of metastatic adenocarcinoma of unknown primary mimicking cerebellopontine angle tumor on the magnetic resonance image

This report presented a case of sudden profound bilateral sensorineural hearing loss with progressive facial diparesis in a 64-year-old woman. The magnetic resonance imaging (MRI) finding mimicked bilateral masses in the cerebellopontine angle (CPA) in an absence of clinical meningeal or parenchymal involvements at the first presentation. Surgical biopsy and histopathologic finding identified masses secondary to direct invasion of adenocarcinoma of gastrointestinal origin. Many investigations could not discover the primary site of the metastatic adenocarcinoma. Grave prognosis was observed in all cases reported including ours; the patient died 10 weeks after onset of symptoms.     

Synthesis of 2‐(2‐oxo‐2H‐chromen‐4‐yl)acetamides as potent acetylcholinesterase inhibitors and molecular insights into binding interactions

Sixteen novel coumarin‐based compounds are reported as potent acetylcholinesterase (AChE) inhibitors. The most active compound in this series, 5a (IC₅₀ 0.04 ± 0.01 µM), noncompetitively inhibited AChE with a higher potency than tacrine and galantamine. Compounds 5d , 5j , and 5 m showed a moderate antilipid peroxidation activity. The compounds showed cytotoxicity in the same range as the standard drugs in HEK‐293 cells. Molecular docking demonstrated that 5a acted as a dual binding site inhibitor. The coumarin moiety occupied the peripheral anionic site and showed π‐π interaction with Trp278. The tertiary amino group displayed significant cation‐π interaction with Phe329. The aromatic group showed π‐π interaction with Trp83 at the catalytic anionic site. The long chain of methylene lay along the gorge interacting with Phe330 via hydrophobic interaction. Molecular docking was applied to postulate the selectivity toward AChE of 5a in comparison with donepezil and tacrine. Structural insights into the selectivity of the coumarin derivatives toward huAChE were explored by molecular docking and 3D QSAR and molecular dynamics simulation for 20 ns. ADMET analysis suggested that the 2‐(2‐oxo‐2H‐chromen‐4‐yl)acetamides showed a good pharmacokinetic profile and no hepatotoxicity. These coumarin derivatives showed high potential for further development as anti‐Alzheimer agents.     

Health and Health Care System for Older Persons

Thailand has now reached a new demographic turning point with the advent of an ageing society. Improvements in the health care system and technology advancement over recent decades mean that Thais can now enjoy better health in old age than previously. Life expectancy at birth for the Thai population has been increasing steadily, and there has been an improvement among older persons in all aspects of health behaviors. Even though the majority of Thai elderly are sufficiently healthy to take care of themselves, there are an increasing number of elderly people who have difficulty with essential daily activities, leading to problems with disability and dependency. Non communicable diseases such as hypertension, diabetes mellitus, dyslipidemia, osteoarthritis, cardio-cerebrovascular diseases and tumor are some of the major health problems confronting older Thais. Due a higher incidence of illness and chronic conditions as compared to young people, the elderly typically require different types of care and health services. As Thailand becomes an ageing society, health services and proper care systems specifically for the elderly group need to be prepared and well established. Given the far greater likelihood of chronic conditions and disabilities among older persons compared to the rest of population, pressures on long-term care facilities and services will increase enormously. The issue of ageing should be given a high priority in both local and national government agendas. All sectors should be involved in adjusting care systems and programs to accommodate the rapid growth of older persons and the relative balance of age groups within the population. It will be crucial for the health sectors to provide services oriented towards geriatric and long-term care issues.