Midface hypoplasia in syndromic craniosynostosis: predicting craniofacial growth via a novel regression model from anatomical morphometric analysis.

Midface hypoplasia in syndromic craniosynostosis (SC) may lead to serious respiratory issues. The aim of this study was to analyse the morphometric correlation between midface and cranial base parameters in paediatric SC patients in order to formulate predictive regression models. The computed tomography scans of 18 SC patients and 20 control were imported into Materialise Mimics Medical version 21.0 software for the measurement of multiple craniofacial landmarks and correlation analysis. The results showed a strong correlation of anterior cranial base (SN), posterior cranial base (SBa), and total cranial base (NBa) (r = 0.935) to maxilla length and width (ZMR-ZML) (r = 0.864). The model of NBa = - 1.554 + 1.021(SN) + 0.753(SBa) with R2 = 0.875 is proposed to demonstrate the development of the cranial base that causes a certain degree of midface hypoplasia in SC patients. The formula is supported using a prediction model of ZMR-ZML = 5.762 + 0.920(NBa), with R2 = 0.746. The mean absolute difference and standard deviation between the predicted and true NBa and ZMR-ZML were 2.08 ± 1.50 mm and 3.11 ± 2.32 mm, respectively. The skeletal growth estimation models provide valuable foundation for further analysis and potential clinical application.

Is a symmetrical face really attractive?

Facial symmetry plays an important role in facial attractiveness and is one of the major criteria used to determine attractiveness in humans. In craniomaxillofacial surgery, facial symmetry is one of the main considerations. The aim of this study was to determine anthropometric measurements quantitatively and investigate the relationship between facial symmetry and attractiveness in a local Malay population. The study included 30 photographed Malay individuals and 100 photograph assessors, all aged between 18 and 26 years. The assessors indicated their preferences regarding the more attractive face on original and manipulated (symmetrical face) photographs. None of the photographed subjects had a perfectly symmetrical face (asymmetry index (AI) of 0%); 33.3% of the photographed subjects had an AI in the range of 1.6-2.0%. The majority of assessors chose the manipulated symmetrical face as the most attractive (manipulated photograph selected in 91.2% of cases). As facial symmetry is considered a critical factor in attractiveness, it is beneficial to consider balance and symmetry prior to facial reconstruction. The AI values found in this study may be useful as guidance to determine the normal minimum balance of facial symmetry. No AI values indicating perfect symmetry were observed for the unedited facial anthropometric measurements. However, the projection of a perfectly symmetrical face does influence the perception of facial attractiveness.

Relationship between various cytokines implicated in asthma.

Asthma is a complex disorder involving immunologic, environmental, genetic and other factors. Today, asthma is the most common disease encountered in clinical medicine in both children and adults worldwide. Asthma is characterized by increased responsiveness of the tracheobronchial tree resulting in chronic swelling and inflammation of the airways recognized to be controlled by the T-helper 2 (Th2) lymphocytes, which secrete cytokines to increase the production of IgE by B cells. There are many cytokines implicated in the development of the chronic inflammatory processes that are often observed in asthma. Ultimately, these cytokines cause the release of mediators such as histamine and leukotrienes (LT), which in turn promote airway remodeling, bronchial hyperresponsiveness and bronchoconstriction. The CD4+ T-lymphocytes from the airways of asthmatics express a panel of cytokines that represent the Th2 cells. The knowledge derived from numerous experimental and clinical studies have allowed physicians and scientists to understand the normal functions of these cytokines and their roles in the pathogenesis of asthma. The main focus of this review is to accentuate the relationship between various cytokines implicated in human asthma. However, some key findings from animal models will be highlighted to support the discoveries from clinical studies.

Improvement in baroreflex control of renal sympathetic nerve activity in obese Sprague Dawley rats following immunosuppression.

AIM: This investigation explored the hypothesis that in obesity an inflammatory response in the kidney contributed to a renal nerve-dependent blunting of the baroreflex regulation of renal sympathetic nerve activity. METHODS: Rats received a normal (12% kcal) or high-fat (45% kcal) diet for 8 weeks plus daily injections of vehicle (0.9% NaCl i.p) or tacrolimus (0.25 mg kg-1 day-1 i.p) from weeks 3-8. Following anaesthesia, left renal sympathetic nerve activity was recorded, baroreflex gain curves were generated, by infusing phenylephrine and sodium nitroprusside, and cardiopulmonary baroreceptors challenged by infusing a saline load. RESULTS: The high-fat diet elevated weight gain and adiposity index by 89 and 129% (both, P < 0.001). Mean blood pressure (132 ± 4 vs 103 ± 5 mmHg), fractional noradrenaline excretion and creatinine clearance (5.64 ± 0.55 vs 3.32 ± 0.35 mL min-1 kg-1 ) were 28, 77 and 69% higher (all P < 0.05), but urine flow and fractional sodium excretions were 42 and 72% (both P < 0.001) lower compared to normal rats. Plasma and renal TNF-α and IL-6 concentrations were fourfold to fivefold (P < 0.001) and 22 and 20% higher (both, P < 0.05), in obese rats but normalized following tacrolimus. In obese rats, baroreflex sensitivity was reduced by 80% (P < 0.05) but restored by renal denervation or tacrolimus. Volume expansion reduced renal sympathetic nerve activity by 54% (P < 0.001) in normal and obese rats subjected to renal denervation and tacrolimus, but not in obese rats with an intact renal innervation. CONCLUSION: Obesity induced a renal inflammation and pointed to this being both the origin of autonomic dysregulation and a potential focus for targeted therapy.

Soil-Transmitted Helminths in Malaysia landscape: an aborigines study.

Soil-transmitted helminths (STH) is a group of parasitic nematodes, including Trichuris trichiura, Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus, which can cause gastrointestinal disorders in humans. STH is prevalent among neglected communities in both developing and developed countries. This present study aims to determine the current prevalence of STH infections in Aboriginal population after mass delivering of antihelminthic drugs was proposed by WHO in 2005 and a health education learning package (HELP) was initiated in Malaysia in 2012. A total of 235 human fecal samples were collected and a pre-tested questionnaire was given to gather information about the socio-demographic of the Aborigine communities living in Kedah and Selangor, Malaysia. The samples were screened by a direct-fecal smear and confirmed by formalin-ether sedimentation methods. From human faeces, 81.7% was found to be infected with one or more STH species. T. trichiura was the most commonly detected (76.6%), followed by hookworms (26.4%) and A. lumbricoides (19.1%). Triple infections were found in 6.4% of the studied population. Univariate analysis showed that individuals with age group, male, presence of indoor toilet, family size with <7 members and bad living habits (i.e., without antihelminthic drugs) were significantly associated with STH infections. The analysis further showed that walking barefoot was the significant contributing factor to hookworm infections. The high prevalence of human STH infections is alarming. Thus, the urgency in implementing health education related behavioral practice and hygiene to reduce disease burden in these rural communities are a crucial need.

Soil-Transmitted Helminths in Malaysia landscape: an aborigines study

Soil-transmitted helminths (STH) is a group of parasitic nematodes, including Trichuris trichiura, Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus, which can cause gastrointestinal disorders in humans. STH is prevalent among neglected communities in both developing and developed countries. This present study aims to determine the current prevalence of STH infections in Aboriginal population after mass delivering of antihelminthic drugs was proposed by WHO in 2005 and a health education learning package (HELP) was initiated in Malaysia in 2012. A total of 235 human fecal samples were collected and a pre-tested questionnaire was given to gather information about the socio-demographic of the Aborigine communities living in Kedah and Selangor, Malaysia. The samples were screened by a direct-fecal smear and confirmed by formalin-ether sedimentation methods. From human faeces, 81.7% was found to be infected with one or more STH species. T. trichiura was the most commonly detected (76.6%), followed by hookworms (26.4%) and A. lumbricoides (19.1%). Triple infections were found in 6.4% of the studied population. Univariate analysis showed that individuals with age group, male, presence of indoor toilet, family size with <7 members and bad living habits (i.e., without antihelminthic drugs) were significantly associated with STH infections. The analysis further showed that walking barefoot was the significant contributing factor to hookworm infections. The high prevalence of human STH infections is alarming. Thus, the urgency in implementing health education related behavioral practice and hygiene to reduce disease burden in these rural communities are a crucial need.

Potential use of cord blood for Hb E hemoglobinopathy screening programme using capillary electrophoresis.

BACKGROUND: Thalassemia and hemoglobinopathies are inherited red blood cell disorders found worldwide. Hemoglobin (Hb) E disorder is one of the hemoglobinopathies known to have the high prevalence in South East Asia. Most of transfusion-dependent thalassemias were genotypically compound heterozygous Hb E/ ß-thalassemia. In Malaysia, the national screening program for thalassemia was implemented for early pregnancy or secondary school girls; however many participants do not turn-up and missed the screening test. Screening for thalassemia using samples from cord blood is an alternative choice as it is a readily available source of blood and hence early detection of the disease. The purpose of this study was to determine the potential use of cord blood for the screening of HbE hemoglobinopathy by using capillary electrophoresis (CE). METHODS: Cord blood samples were collected from 300 newborns of healthy mothers. Hematological parameters were determined and hemoglobin quantitation for all cord blood samples were performed using capillary electrophoresis system (CES) and high performance liquid chromatography (HPLC). RESULTS: Majority of cord blood samples (63%) revealed Hb AF followed by Hb AFA2 (20%). Hb AFE was detected in 10.7% with the mean value of Hb E ranging from 2.3%-11.1%. CONCLUSION: Hemoglobin E was detected in cord blood using capillary electrophoresis system. It can be recommended in areas where Hb E/ß is prevalent. Implementation of a screening strategy using CE on cord blood sampling will identify the disease early. With regular follow-up on these patients, the status of their disease can be determined earlier and appropriate management implemented.

Enhanced expression of endothelial nitric oxide synthase in the myocardium ameliorates the progression of left ventricular hypertrophy in L-arginine treated Wistar-Kyoto rats.

The present study investigated the role of endothelial nitric oxide synthase (eNOS) enzyme in the development of left ventricular hypertrophy (LVH) in Wistar-Kyoto rats. The effect of L-arginine administration on cardiac structure, arterial stiffness, renal and systemic hemodynamic parameters was studied and the change in expression of eNOS and cystathione γ lyase (CSE) in the myocardium of LVH rats was evaluated. LVH was induced using isoprenaline (5 mg/kg, S.C.) and caffeine (62 mg/L in drinking water) for 14 days. Following to that, L-arginine (1.25 g/L in drinking water) was given for 5 weeks as a donor of NO. eNOS and CSE gene expressions were down regulated in the LVH group by about 35% and 67% respectively when compared to control. However, in the LVH group treated with L-arginine there was up regulation of eNOS by almost 27% and down regulation in CSE by 24% when compared to control (all P < 0.05). Heart index and H2S plasma levels were reduced by almost 53% in the L-arginine treated LVH group compared to the control (all P < 0.05). Mean arterial pressure, heart rate and pulse wave velocity were reduced while renal blood perfusion increased in L-arginine treated LVH rats compared to their untreated counterparts (all P < 0.05). The enhanced expression of eNOS in L-arginine treated LVH rats resulted in the amelioration of oxidative and haemodynamic parameters suggesting that NO system is an important therapeutic target in cardiac and LV hypertrophies.

Genetic variation in Rhodomyrtus tomentosa (Kemunting) populations from Malaysia as revealed by inter-simple sequence repeat markers.

Kemunting (Rhodomyrtus tomentosa) from the Myrtaceae family, is native to Malaysia. It is widely used in traditional medicine to treat various illnesses and possesses significant antibacterial properties. In addition, it has great potential as ornamental in landscape design. Genetic variability studies are important for the rational management and conservation of genetic material. In the present study, inter-simple sequence repeat markers were used to assess the genetic diversity of 18 R. tomentosa populations collected from ten states of Peninsular Malaysia. The 11 primers selected generated 173 bands that ranged in size from 1.6 kb to 130 bp, which corresponded to an average of 15.73 bands per primer. Of these bands, 97.69% (169 in total) were polymorphic. High genetic diversity was documented at the species level (H(T) = 0.2705; I = 0.3973; PPB = 97.69%) but there was a low diversity at population level (H(S) = 0.0073; I = 0 .1085; PPB = 20.14%). The high level of genetic differentiation revealed by G(ST) (73%) and analysis of molecular variance (63%), together with the limited gene flow among population (N(m) = 0.1851), suggests that the populations examined are isolated. Results from an unweighted pair group method with arithmetic mean dendrogram and principal coordinate analysis clearly grouped the populations into two geographic groups. This clear grouping can also be demonstrated by the significant Mantel test (r = 0.581, P = 0.001). We recommend that all the R. tomentosa populations be preserved in conservation program.

Development of SNP markers and their application for genetic diversity analysis in the oil palm (Elaeis guineensis).

The genetic evaluation of oil palm germplasm collections is required for insight into the variability among populations. The information obtained is also useful for incorporating new genetic materials into current breeding programs. Single nucleotide polymorphisms (SNPs) have been widely used in many plant genetic studies due to the availability of large numbers of genomic sequences and expressed sequence tags. The present study examined 219 oil palms collected from two natural Angolan populations, a few hundred kilometers apart. A total of 62 SNPs were designed from oil palm genomic sequences and converted to cleaved amplified polymorphic sequence (CAPS). Of these, nine were found to be informative across the two populations. The nine informative SNPs revealed mean major allele frequency of 0.693. The average expected and observed heterozygosities were 0.398 and 0.400, respectively. The mean polymorphism information content was 0.315 (ranging between 0.223 and 0.375). None of the loci deviated from Hardy-Weinberg equilibrium and no rare alleles were detected. In cluster analysis using unweighted pair group method with arithmetic, the 219 oil palms fell into two clusters. This was further supported by the population structure analysis result (K = 2), suggesting that the samples were divided into two main genetic groups. However, the two groups did not coincide with the geographic populations. Analysis of molecular variance indicated that within-population variation contributed 93% of the total genetic variation. This study showed that SNP-based CAPS markers are useful for studying the genetic diversity of oil palm and have potential application for marker-trait association studies.

Obesity depresses baroreflex control of renal sympathetic nerve activity and heart rate in Sprague Dawley rats: role of the renal innervation.

AIM: This study investigated the role of the renal innervation in arterial and cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats fed a high-fat diet to induce obesity. METHODS: Rats received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On day 61, rats were anesthetized and prepared for recording left RSNA. In one group, the renal nerves remained intact, while in the other, both kidneys were denervated. Baroreflex gain curves for RSNA and HR were generated by increasing and decreasing blood pressure. Low-pressure baroreceptors were challenged by infusing a saline load. RESULTS: Mean blood pressure was 135 mmHg in the fat-fed and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower, respectively, in the fat-fed compared to normal rats. In fat-fed rats with innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by 73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats. CONCLUSION: Feeding a high-fat diet caused hypertension associated with dysregulation of the arterial and cardiopulmonary baroreflexes which was dependent on an intact renal innervation. This suggests that in obese states neural signals arising from the kidney contribute to a deranged autonomic control.

Assessing the genetic relationships of Curcuma alismatifolia varieties using simple sequence repeat markers.

The genus Curcuma is a member of the ginger family (Zingiberaceae) that has recently become popular for use as flowering pot plants, both indoors and as patio and landscape plants. We used PCR-based molecular markers (SSRs) to elucidate genetic variation and relationships between five varieties of Curcuma (Curcuma alismatifolia) cultivated in Malaysia. Of the primers tested, 8 (of 17) SSR primers were selected for their reproducibility and high rates of polymorphism. The number of presumed alleles revealed by the SSR analysis ranged from two to six alleles, with a mean value of 3.25 alleles per locus. The values of HO and HE ranged from 0 to 0.8 (mean value of 0.2) and 0.1837 to 0.7755 (mean value of 0.5102), respectively. Eight SSR primers yielded 26 total amplified fragments and revealed high rates of polymorphism among the varieties studied. The polymorphic information content varied from 0.26 to 0.73. Dice's similarity coefficient was calculated for all pairwise comparisons and used to construct an unweighted pair group method with arithmetic average (UPGMA) dendrogram. Similarity coefficient values from 0.2105 to 0.6667 (with an average of 0.4386) were found among the five varieties examined. A cluster analysis of data using a UPGMA algorithm divided the five varieties/hybrids into 2 groups.

A preliminary report on ants (Hymenoptera: Formicidae) recovered from forensic entomological studies conducted in different ecological habitats in Malaysia.

This study reported the ant species that were recovered from monkey carcasses in three different ecological habitats in Malaysia. The study was conducted from 9 May - 10 October 2007, 6 May - 6 August 2008 and 26 May - 14 July 2009 in forested area (Gombak, Selangor), coastal area (Tanjong Sepat, Selangor) and highland area (Bukit Cincin, Pahang), respectively. Monkey carcass was used as a model for human decomposition in this study. A total of 4 replicates were used in each of the study sites. Ants were observed to prey on eggs, larvae, pupae and newly emerged flies. This study found that ant species could be found at all stages of decomposition, indicating that ants were not a significant indicator for faunal succession. However, different species of ants were obtained from monkey carcasses placed in different ecological habitats. Cardiocondyla sp. was only found on carcasses placed in the coastal area; while Pheidole longipes, Hypoponera sp. and Pachycondyla sp. were solely found on carcasses placed in the highland area. On the other hand, Pheidologeton diversus and Paratrechina longicornis were found in several ecological habitats. These data suggests that specific ant species can act as geographic indicators for different ecological habitats in forensic entomology cases in Malaysia.

Renal denervation restores the baroreflex control of renal sympathetic nerve activity and heart rate in Wistar-Kyoto rats with cisplatin-induced renal failure.

AIM: There is evidence that in chronic renal failure, the sympathetic nervous system is activated. This study investigated the role of the renal innervation in suppressing high- and low-pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin-induced renal failure. METHODS: Renal failure was induced using cisplatin (5 mg kg(-1) , i.p.) and the rats used 7 days later. Groups of rats were anaesthetized and prepared for measurement of renal sympathetic nerve activity and heart rate. Acute unilateral or bilateral renal denervation was performed, and renal sympathetic nerve activity and heart rate baroreflex gain curves were generated while the cardiopulmonary receptors were stimulated using an acute saline volume load. RESULTS: Cisplatin administration reduced (P < 0.05) glomerular filtration rate by 27%, increased sodium fractional excretions fourfold, plasma creatinine and kidney index by 39 and 30% respectively, (all P < 0.05) compared with control rats. In the renal failure rats, baroreflex sensitivity for renal sympathetic nerve activity and heart rate was reduced (P < 0.05) by 29% and 27% (both P < 0.05) compared with control animals. Bilateral, but not unilateral, renal denervation restored baroreflex sensitivity to normal values. Volume expansion reduced (P < 0.05) renal sympathetic nerve activity by 34% in control rats, but remained unchanged in the renal failure rats. Unilateral and bilateral renal denervation progressively restored the volume expansion induced renal sympathoinhibition to control values. CONCLUSION: These findings reveal a significant role of the renal sensory innervation in cisplatin-damaged kidneys which blunt the normal baroreflex control of renal sympathetic nerve activity.

Ectopic inferior vena cava thrombus secondary to a tubo-ovarian abscess.

Inferior vena cava (IVC) thrombosis typically arises distally from a thrombophlebitic extension in the pelvis or the lower extremities. It may also occur from propagation of an ovarian vein thrombosis as a result of gynaecological disorders such as pelvic inflammatory disease, endometritis or from pelvic surgeries. In this report, we present an interesting case of a tubo-ovarian abscess with an ectopic IVC thrombus. The approach to management in such cases is also highlighted.

Successful treatment of isolated fibular bone metastasis in a uterine endometrial cancer of clear cell carcinoma.

Clear cell carcinoma of the endometrium is an uncommon histological subtype and isolated metastasis to bone is rare. The authors present a case of a 61-year-old woman who underwent laparoscopic staging surgery for clear cell carcinoma of uterine endometrium (FIGO Stage IB) and early recurrence with isolated fibular bone metastasis three months later. With salvage radiotherapy (RT), she remains disease-free after 46 months. Curative-intended treatment with RT is possible as in this case.

Composition and sources of aliphatic lipids and sterols in sediments of a tropical island, southern South China Sea: preliminary assessment.

Near-shore surface sediment was collected from five stations off Redang Island located on the eastern coast of Peninsular Malaysia. Freeze-dried sediments were Soxhlet extracted and then fractionated using column chromatography into aliphatic and polar fractions. Determination of these fractions was carried out using gas chromatography mass spectrometry. The concentration of total resolved aliphatic hydrocarbons in sediments ranged from 157 to 308 ng/g. The distribution of aliphatic fraction showed the presence of n-alkanes ranging from nC15 to nC33 with a minor odd-to-even predominance exhibiting carbon maximum, depending on station, at nC17, nC26, nC29 or nC31. Calculation of Carbon Preference Index (CPI) for CPI(15-33) gave values ranging from 1.09 to 1.46. n-Alkanol in all sediment exhibits even-to-odd carbon predominance ranging from nC16 to nC28 and maximising at nC22. n-Fatty acids distribution ranged from nC14 to nC24 with a dominant maximum at nC16 and exhibiting high values of short chain fatty acids (≤nC20) to long chain fatty acids (>nC20) ratios. Unsaturated fatty acids, particularly nC16:1 and nC18:1 is also ubiquitous in all samples. Cholesterol is the most abundant compound amongst the sterol group ranging from 42.8 to 62.6% of the total sterols. ß-Sitosterol, brassicasterol and stigmasterol, are also present but of relatively lower amount. These observations suggest that the aliphatic lipids and sterols in the study area originate, mainly, from biogenic sources of marine microbial with minor contribution from epiticular waxes of terrestrial plants.

Sustainable complete remission in recurrence yolk sac tumor patient treated with tandem high-dose chemotherapy and autologous stem cell.

A 21-year-old lady diagnosed with Stage 3 ovarian yolk sac tumor (YST) underwent primary cytoreductive fertility sparing surgery, followed by conventional courses of platinum-based chemotherapy and etoposide. Recurrence at cul-da-sac was noted after a short period of remission and secondary debulking performed followed by four cycles of conventional chemotherapy. The patient's disease progressed despite courses of treatments. A joint team management including a hematologist was commenced following the failure of conventional chemotherapies. Two cycles of high-dose chemotherapy (HDCT) with ifosfamide/cisplatin/etoposide (ICE) regimen, followed by autologous stem cell transplantation (ASCT) were given. With this salvage treatment, she remained in complete remission and disease-free for more than 30 months, while maintaining her reproductive function. These approaches appear to be effective as a salvage treatment in selected cases of patients with ovarian germ cell tumor, especially those who failed primary conventional chemotherapy.

Neuropsychiatric adverse events of varenicline: a systematic review of published reports.

INTRODUCTION: Over the past years, the impact of varenicline in patients with mental illness has been debated as serious neuropsychiatric adverse events (AEs) have been reported with varenicline use. AIM: To identify and summarize published case reports of neuropsychiatric AEs ascribed to varenicline and to determine potential risk factors for these AEs. METHODS: A literature search of MEDLINE, the Cochrane Library, EMBASE, and PsychInfo database was conducted for case reports concerning the neuropsychiatric AEs of varenicline published in English from 2006 (approval year by the US Food and Drug Administration and the Dutch Medicines Evaluation Board) to January 1, 2012. RESULTS: We identified 25 published cases. In most reports, patients had been admitted to psychiatric hospitals with serious neuropsychiatric AEs due to varenicline. The average patient age was 46.4 years, and 56% were men; 68% of patients had a psychiatric history. The onset of symptoms started 2 days to 3 months after the initiation of varenicline. One report described completed suicide in a man with no psychiatric history. In most cases (84%), the neuropsychiatric symptoms resolved after the discontinuation of varenicline. Analysis of all reports using the Naranjo causality scale, a method for estimating the probability of adverse drug reactions, indicated probable causality in 76% of the cases and definite causality in 12% of cases. CONCLUSION: Varenicline is associated with an increased risk of serious neuropsychiatric AEs, especially in patients with a psychiatric illness. It is strongly recommended that varenicline be administered only to mentally stable patients and under close monitoring.