Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review.

Nowadays, the scientific community has focused on dealing with different kinds of diseases by exploring the chemistry of various heterocycles as novel drugs. In this connection, medicinal chemists identified carbonic anhydrases (CA) as one of the biologically active targets for curing various diseases. The widespread distribution of these enzymes and the high degree of homology shared by the different isoforms offer substantial challenges to discovering potential drugs. Medicinal and synthetic organic chemists have been continuously involved in developing CA inhibitors. This review explored the chemistry of different heterocycles as CA inhibitors using the last 11 years of published research work. It provides a pathway for young researchers to further explore the chemistry of a variety of synthetic as well as natural heterocycles as CA inhibitors.

Comparative life cycle assessment of environmental impacts and economic feasibility of tomato cultivation systems in northern plains of India.

To meet the growing demand for vegetable production and promote sustainable agriculture, it is imperative to implement effective input management and adopt eco-friendly farming practices. This study aims to compare the environmental impacts of conventional and organic tomato cultivation in the northern plains of India. This study utilizes SimaPro 9.1.1 software for a comprehensive cradle-to-farm gate Life Cycle Assessment (LCA), assessing production stages, identifying key environmental factors, and incorporating ReCiPe Midpoint and Endpoint methods with one-hectare as a functional unit. Findings reveal that conventional cultivation is more affected by fertilizer application and transplanting, while organic cultivation emphasizes transplanting and irrigation. Organic cultivation contributes 904.708 kg CO2, while conventional cultivation contributes 1307.917 kg CO2 to Global Warming potential. Switching to organic cultivation leads to a significant 35.04% decrease in all impact categories. Using the endpoint method, organic cultivation achieves a notable 27.16% reduction, scoring 58.30 compared to conventional cultivation's 80.04. The LCA analysis of tomato cultivation highlights Fertilizer application as the predominant environmental concern, emphasizing the need for sustainable techniques to minimize waste and mitigate environmental impacts. This study recommends imposing restrictions on fertilizer and pesticide use and formulating effective policies to promote the adoption of sustainable practices.

Tuning between Nuclear Organization and Functionality in Health and Disease.

The organization of eukaryotic genome in the nucleus, a double-membraned organelle separated from the cytoplasm, is highly complex and dynamic. The functional architecture of the nucleus is confined by the layers of internal and cytoplasmic elements, including chromatin organization, nuclear envelope associated proteome and transport, nuclear-cytoskeletal contacts, and the mechano-regulatory signaling cascades. The size and morphology of the nucleus could impose a significant impact on nuclear mechanics, chromatin organization, gene expression, cell functionality and disease development. The maintenance of nuclear organization during genetic or physical perturbation is crucial for the viability and lifespan of the cell. Abnormal nuclear envelope morphologies, such as invagination and blebbing, have functional implications in several human disorders, including cancer, accelerated aging, thyroid disorders, and different types of neuro-muscular diseases. Despite the evident interplay between nuclear structure and nuclear function, our knowledge about the underlying molecular mechanisms for regulation of nuclear morphology and cell functionality during health and illness is rather poor. This review highlights the essential nuclear, cellular, and extracellular components that govern the organization of nuclei and functional consequences associated with nuclear morphometric aberrations. Finally, we discuss the recent developments with diagnostic and therapeutic implications targeting nuclear morphology in health and disease.

Alpha-1-antitrypsin in serum exosomes and pericardial fluid exosomes is associated with severity of rheumatic heart disease.

Rheumatic heart disease (RHD) is an autoimmune sequel of pharyngitis and rheumatic fever that leads to permanent heart valve damage, especially the mitral valves. The mitral valves, which are responsible for the binding of auto-antibodies during immune response generation, lead to valve scarring and eventually valves dysfunction. Recently, exosomes (EXOs), the nano-sized vesicles, which range in size from 30 to 150 nm, are reported in various cardiovascular physiological and pathological processes. These vesicles are found in several body fluids such as plasma, serum, and also in cell culture media. Exosomal cargo contains proteins, which are taken up by the recipient cells and modulate the cellular characteristics. The role of exosomal proteins in RHD is still obscure. Hence, the present study has been designed to unveil the exosomal proteins in disease severity during RHD. In this study, the exosomes were isolated from biological fluids (serum and pericardial fluid) of RHD patients as well as from their respective controls. Protein profiling of these isolated exosomes revealed that alpha-1 antitrypsin is up-regulated in the biological fluids of RHD patients. The enhanced levels of exosomal alpha-1 antitrypsin, were further, validated in biological samples and mitral valve tissues of RHD patients, to correlate with the disease severity. These findings suggest an association of increased levels of exosomal alpha-1 antitrypsin with the RHD pathogenesis.

A Study on Synthesis of Chalcone Derived -5- Membered Isoxazoline and Isoxazole Scaffolds.

Chalcone-derived isoxazole scaffolds remain the central focus due to their greater biological, clinical, and pharmacological properties. The present study reviews the synthesis of various chalcone derived - 5- membered isoxazoline and isoxazole scaffolds with the available literature until 2021.

Perinatal outcome in monochorionic twin pregnancies after selective fetal reduction using radiofrequency ablation.

OBJECTIVE: To study the perinatal outcomes in women with complicated monochorionic twin pregnancies undergoing selective fetal reduction using radiofrequency ablation (RFA). METHODS: This retrospective study included 44 patients with monochorionic twin pregnancies, between 14 and 28 weeks of pregnancy, who underwent RFA for selective fetal reduction. Perinatal and maternal outcomes and procedure-related complications were analyzed. RESULTS: The procedure was technically successful in all 44 cases. Indications for selective fetal reduction included twin-to-twin transfusion syndrome (52.3%), twin reversed arterial perfusion (20.5%), twins discordant for anomaly (15.9%), and selective fetal growth restriction (11.4%). Median gestational age at procedure was 222/7  weeks (range 14-266/7 ). Live birth rate was 77.3% with three neonatal deaths; so overall survival was 70.5%. Median procedure-to-delivery interval was 123/7  weeks (range 24/7 -23). There were eight losses before 24 weeks of pregnancy, which included two co-twin deaths. Median gestational age at delivery was 35 weeks (interquartile range 321/7 -37 weeks). The preterm delivery rate was 66.7% (24/36) and preterm prelabor rupture of membranes (PPROM) occurred in 22.7% (10/44) of patients. CONCLUSION: Selective fetal reduction using RFA is safe and effective in complicated monochorionic pregnancies. However, the rates of PPROM and preterm delivery remain high.

Novel p-Functionalized Chromen-4-on-3-yl Chalcones Bearing Astonishing Boronic Acid Moiety as MDM2 Inhibitor: Synthesis, Cytotoxic Evaluation and Simulation Studies.

BACKGROUND: Novel 4-[3-(6/7/8-Substituted 4-Oxo-4H-chromen-3-yl)acryloyl]phenylboronic acid derivatives (5a-h) as well as other 6/7/8-substituted-3-(3-oxo-3-(4-substitutedphenyl) prop-1-enyl)-4H-chromen-4-one derivatives (3a-u) have been designed as p53-MDM2 pathway inhibitors and reported to possess significant cytotoxic properties against several cancer cell lines. OBJECTIVES: The current project aims to frame the structure-anticancer activity relationship of chromen-4-on-3-yl chalcones (3a-u/5a-h). In addition, docking studies were performed on these chromeno-chalcones in order to have an insight into their interaction possibilities with MDM2 protein. METHODS: Twenty-nine chromen-4-on-3-yl chalcone derivatives (3a-u/5a-h) were prepared by utilizing silica supported-HClO4 (green route with magnificent yield) and tested against four cancer cell lines (HCT116, MCF-7, THP-1, NCIH322). RESULTS: Among the series 3a-u, compound 3b exhibited the highest anticancer activity (with IC50 values ranging from 8.6 to 28.4 µM) overall against tested cancer cell lines. Interestingly, para- Boronic acid derivative (5b) showed selective inhibition against colon cancer cell line, HCT-116 with an IC50 value of 2.35 µM. Besides the emblematic hydrophobic interactions of MDM2 inhibitors, derivative 5b was found to exhibit extra hydrogen bonding with GLN59 and GLN72 residues of MDM2 in molecular dynamics (MD) simulation. All the compounds were virtually nontoxic against normal fibroblast cells. CONCLUSION: Novel compounds were obtained with good anticancer activity especially 6- Chlorochromen-4-one substituted boronic acid derivative 5b. The molecular docking study proposed good activity as a MDM-2 inhibitor suggesting hydrophobic as well as hydrogen bonding interactions with MDM2.

Musculoskeletal disorders among insurance office employees: A case study.

BACKGROUND: Insurance employees in India are overworked, and their jobs demand prolonged sitting hours in the office; this can lead to musculoskeletal disorders through consistent stress on the musculoskeletal system. The present study includes implications for the reduction of work-related musculoskeletal disorders to minimise sick leaves and medical expenses. OBJECTIVE: This study aimed to determine the prevalence of musculoskeletal disorder-related issues among employees working in insurance offices and to analyse the association of pain symptoms with risk factors including demographic, occupational and psychosocial factors. METHODS: The study included 400 employees from different insurance offices. Data were collected using a questionnaire about pain, a flexibility test (sit-and-reach test) and a video-based analysis of working postures using the Rapid Upper Limb Assessment (RULA) method. RESULTS: The prevalence of work-related musculoskeletal symptoms was the highest in the neck (57.2%), shoulders (38.5%), upper back (28.5%) and lower back (46.2%). CONCLUSIONS: A high persistence of musculoskeletal symptoms was observed in the neck, lower back, upper back and shoulders; the presence of these symptoms was strongly associated with predominant factors: assumed awkward posture, body mass index, job demand, RULA score and infrequent rest breaks. Additional research is required for testing the effect of interventions involving stretching exercises and/or installation of ergonomic workstations.

Role of adenylyl cyclase activator in controlling experimental diabetic nephropathy in rats.

The present study aimed to investigate the role of adenylyl cyclase activator in preventing diabetic nephropathy in rats. Renal function parameters, renal hypertrophy, lipid profile, markers of oxidative stress and free radical scavenging activities were assessed. Histopathology was performed to confirm Streptozotocin induced renal morphological changes in diabetic rats. Male Wistar rats were used in the present study to reduce the effect of estrogen. Rats were subjected to high fat diet (HFD) for two weeks followed by low dose of Streptozotocin (STZ) [35 mg/kg, i.p.] to develop experimental diabetic nephropathy in eight weeks. Two weeks treatment with low dose of Forskolin (10 mg/kg) reduced the level of diabetic nephropathy markers but results observed were not significant. Whereas, Forskolin intermediate dose (20 mg/kg) and high dose (30 mg/kg) treated rats significantly attenuated diabetes induced elevated renal function parameters and endogenous antioxidants enzymatic activities. High dose of Forskolin was found to be more effective in attenuating the renal structural and functional abnormalities. Forskolin prevented renal structural and functional abnormalities in diabetic rats. Histopathological evaluation revealed that Forskolin (20 mg/kg and 30 mg/kg) treated diabetic rats demonstrated reduced vacuolar degeneration of tubules and glomerulosclerosis. In the present study, Glibenclamide (0.6 mg/kg) and Atorvastatin (0.5 mg/kg) were used as standard drugs. Our results demonstrated synergistic effects, when high dose of Forskolin was co-administered with standard drugs. In conclusion, treatment with adenylyl cyclase activator, Forskolin in diabetic rats reduced the elevated serum glucose level, biomarkers of renal morphological dysfunction, renal hypertrophy, dyslipidaemia, oxidative stress and improved renal structure, function and enhanced level of endogenous antioxidants. Forskolin has a potential to prevent nephropathy without showing any effect on body weight in diabetic rats.

Effect of household-based drinking water chlorination on diarrhoea among children under five in Orissa, India: a double-blind randomised placebo-controlled trial.

BACKGROUND: Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five. METHODS AND FINDINGS: We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC) tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence) among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC), an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating equations to account for clustering at the household level. The impact of the intervention on weight-for-age z scores (WAZ) was analysed using random effect linear regression. Over the follow-up period, 84,391 child-days of observations were recorded, representing 88% of total possible child-days of observation. The longitudinal prevalence of diarrhoea among intervention children was 1.69% compared to 1.74% among controls. After adjusting for clustering within household, the prevalence ratio of the intervention to control was 0.95 (95% CI 0.79-1.13). The mean WAZ was similar among children of the intervention and control groups (-1.586 versus -1.589, respectively). Among intervention households, 51% reported their child's drinking water to be treated with the tablets at the time of visit, though only 32% of water samples tested positive for residual chlorine. Faecal contamination of drinking water was lower among intervention households than controls (geometric mean TTC count of 50 [95% CI 44-57] per 100 ml compared to 122 [95% CI 107-139] per 100 ml among controls [p<0.001] [n = 4,546]). CONCLUSIONS: Our study was designed to overcome the shortcomings of previous double-blinded trials of household water treatment in low-income settings. The sample size was larger, the follow-up period longer, both urban and rural populations were included, and adherence and water quality were monitored extensively over time. These results provide no evidence that the intervention was protective against diarrhoea. Low compliance and modest reduction in water contamination may have contributed to the lack of effect. However, our findings are consistent with other blinded studies of similar interventions and raise additional questions about the actual health impact of household water treatment under these conditions. TRIAL REGISTRATION: ClinicalTrials.govNCT01202383 Please see later in the article for the Editors' Summary.

Occupational noise-induced hearing loss in Indian steel industry workers: an exploratory study.

OBJECTIVE: The present study focused on exploring the current level of hearing protection and subsequently determined the prevalence of occupational noise-induced hearing loss among casting and forging industry workers. BACKGROUND: The casting and forging industry provides employment to a significant portion of the population. METHOD: The level of hearing protection was assessed through questionnaire survey of 572 workers. Out of these workers, 165 and another control group of 57 participants were assessed by formal audiometry. Audiometric tests were conducted at frequencies of 1.0 KHz to 8.0 KHz.The occurrence of hearing loss was determined on the basis of a hearing threshold level with a low fence of 25 dB. Student's test and ANOVA were used to compare the various groups; a p value < .05 was considered statistically significant. RESULTS: More than 90% of the workers sampled showed significant hearing loss at medium and high frequencies. The analyses revealed a higher prevalence of significant hearing loss among the forging workers compared with the workers associated with the other activities. CONCLUSIONS: The workers of the Indian steel industry are highly exposed to occupational noise. The majority of workers are not protected from noise-induced hearing loss. There is a need to provide special ear protectors for workers engaged in forging. A complete hearing protection program, including training, audiometry, job rotation, and the use of hearing protection devices, needs to be introduced.

Prevalence of permanent hearing threshold shift among workers of Indian iron and steel small and medium enterprises: a study.

Occupational noise exposure and noise-induced hearing loss (NIHL) have been recognized as a problem among workers in Indian industries. The major industries in India are based on manufacturing. There are appreciable numbers of casting and forging units spread across the country. The objective of this study is to determine the prevalence of permanent hearing threshold shift among the workers engaged in Indian iron and steel small and medium enterprises (SMEs) and compared with control group subjects. As a part of hearing protection intervention, audiometric tests were conducted at low (250-1000 Hz), medium (1500-3000 Hz), and high (4000-8000 Hz) frequencies. The occurrence of hearing loss was determined based on hearing threshold levels with a low fence of 25 dB. Comparisons were made for hearing threshold at different frequencies between the exposed and control groups using Student's t test. ANOVA was used for the comparison of hearing threshold dB at different frequencies among occupation and year of experience. A P value <0.05 was considered as statistically significant. All data were presented as mean value (SD). Over 90% of workers engaged in various processes of casting and forging industry showed hearing loss in the noise-sensitive medium and higher frequencies. Occupation was significantly associated with NIHL, and hearing loss was particularly high among the workers of forging section. The analyses revealed a higher prevalence of significant hearing loss among the forging workers compared to the workers associated with other activities. The study shows alarming signals of NIHL, especially in forging workers. The occupational exposure to noise could be minimized by efficient control measures through engineering controls, administrative controls, and the use of personal protective devices. Applications of engineering and/or administrative controls are frequently not feasible in the developing countries for technical and financial reasons. A complete hearing conservation programme, including training, audiometry, job rotation, and the use of hearing protection devices, is the most feasible method for the protection of industrial workers from prevailing noise in workplace environments in the developing countries.

Removing user fees for basic health services: a pilot study and national roll-out in Afghanistan.

BACKGROUND User fees for primary care tend to suppress utilization, and many countries are experimenting with fee removal. Studies show that additional inputs are needed after removing fees, although well-documented experiences are lacking. This study presents data on the effects of fee removal on facility quality and utilization in Afghanistan, based on a pilot experiment and subsequent nationwide ban on fees. METHODS Data on utilization and observed structural and perceived overall quality of health care were compared from before-and-after facility assessments, patient exit interviews and catchment area household surveys from eight facilities where fees were removed and 14 facilities where fee levels remained constant, as part of a larger health financing pilot study from 2005 to 2007. After a national user fee ban was instituted in 2008, health facility administrative data were analysed to assess subsequent changes in utilization and quality. RESULTS The pilot study analysis indicated that observed and perceived quality increased across facilities but did not differ by fee removal status. Difference-in-difference analysis showed that utilization at facilities previously charging both service and drug fees increased by 400% more after fee removal, prompting additional inputs from service providers, compared with facilities that previously only charged service fees or had no change in fees (P = 0.001). Following the national fee ban, visits for curative care increased significantly (P < 0.001), but institutional deliveries did not. Services typically free before the ban-immunization and antenatal care-had immediate increases in utilization but these were not sustained. CONCLUSION Both pilot and nationwide data indicated that curative care utilization increased following fee removal, without differential changes in quality. Concerns raised by non-governmental organizations, health workers and community leaders over the effects of lost revenue and increased utilization require continued effort to raise revenues, monitor health worker and patient perceptions, and carefully manage health facility performance.

Occupational exposure in small and medium scale industry with specific reference to heat and noise.

This study was undertaken to assess heat and noise exposure and occupational safety practices in small and medium scale casting and forging units (SMEs) of Northern India. We conducted personal interviews of 350 male workers of these units through a comprehensive questionnaire and collected information on heat and noise exposure, use of protective equipment, sweat loss and water intake, working hour. The ambient wet bulb globe temperature (WBGT index) was measured using quest temp 34/36o area heat stress monitor. A-weighted Leq ambient noise was measured using a quest sound level meter "ANSI SI. 43-1997 (R 2002) type-1 model SOUNDPRO SE/DL". We also incorporated OSHA norms for hearing conservation which include - an exchange rate of 5dB(A), criterion level at 90dB(A), criterion time of eight hours, threshold level is equal to 80dB(A), upper limit is equal to 140dB(A) and with F/S response rate. Results of the study revealed that occupational heat exposure in melting, casting, forging and punching sections is high compared to ACGIH/NIOSH norms. Ambience noise in various sections like casting / molding, drop forging, cutting presses, punching, grinding and barreling process was found to be more than 90dB(A). About 95% of the workers suffered speech interference where as high noise annoyance was reported by only 20%. Overall, 68% workers were not using any personal protective equipment (PPE). The study concluded that the proportion of SME workers exposed to high level heat stress and noise (60 - 72 hrs/week) is high. The workers engaged in forging and grinding sections are more prone to noise induced hearing loss (NIHL) at higher frequencies as compared to workers of other sections. It is recommended that there is a strong need to implement the standard of working hours as well as heat stress and noise control measures.

Occupational noise exposure in small scale hand tools manufacturing (forging) industry (SSI) in Northern India.

Occupational noise has been recognized as hazardous for the human beings. A high noise level in forging shops is considered to lower the labour productivity and cause illness however occupational noise is being accepted as an integral part of the job. The present study has been carried out in 5 small scale hand tool forging units (SSI) of different sizes in Northern India in Punjab. Noise levels at various sections were measured. OSHA norms for hearing conservation has been incorporated which includes an exchange rate of 5 dB (A), criterion level at 90 dB (A), criterion time of 8 h, threshold level=80 dB (A), upper limit=140 dB (A) and with F/S response rate. Equivalent sound pressure level (L(eq)) has been measured in various sections of these plants. Noise at various sections like hammer section, cutting presses, punching, grinding and barrelling process was found to be >90 dB (A), which is greater than OSHA norms. A cross-sectional study on the basis of questionnaire has been carried out. The results of which revealed that 68% of the workers are not wearing ear protective equipments out of these 50% were not provided with PPE by the company. About 95% of the workers were suffering speech interference though high noise annoyance was reported by only 20%. It has been established that the maximum noise exposure is being taken by the workers as they are working more than 8h a day for six days per week. More than 90% workers are working 12 to 24 h over time per week which lead to very high noise exposure i.e. 50 to 80% per week higher than exposure time/week in USA or European countries(15, 16)).

Synthesis and cytotoxic activity of some novel polycyclic gamma-butyrolactones.

Baeyer-Villiger oxidation of 5-aryl-7,11,11-trimethyltricyclo[5.4.0.0(3,6)]-undec-1-en-4-ones 4a-h by H(2)O(2) and formic acid in methanol yields mixtures of 3b,7,7-trimethyl-3-phenyl-3,3a,3b,4,5,6,7,8a-octahydro-1H-indeno-[1,2-c]furan-1-ones 8a-h and 3b,7,7-trimethyl-3-phenyl-3,3a,3b,4,5,6,7,8a-octahydro-1H-indeno-[1,2-c]furan-2-ones 9a-h in high yields. The obtained butyrolactones 8a-h display cytotoxic activity against a number of human cancer cells.

Determinants of skilled birth attendant utilization in Afghanistan: a cross-sectional study.

OBJECTIVES: We sought to identify characteristics associated with use of skilled birth attendants where health services exist in Afghanistan. METHODS: We conducted a cross-sectional study in all 33 provinces in 2004, yielding data from 617 health facilities and 9917 women who lived near the facilities and had given birth in the past 2 years. RESULTS: Only 13% of respondents had used skilled birth attendants. Women from the wealthiest quintile (vs the poorest quintile) had higher odds of use (odds ratio [OR] = 6.3; 95% confidence interval [CI] = 4.4, 8.9). Literacy was strongly associated with use (OR = 2.5; 95% CI = 2.0, 3.2), as was living less than 60 minutes from the facility (OR = 1.5; 95% CI = 1.1, 2.0) and residing near a facility with a female midwife or doctor (OR = 1.4; 95% CI = 1.1, 1.8). Women living near facilities that charged user fees (OR = 0.8; 95% CI = 0.6, 1.0) and that had male community health workers (OR = 0.6; 95% CI = 0.5, 0.9) had lower odds of use. CONCLUSIONS: In Afghanistan, the rate of use of safe delivery care must be improved. The financial barriers of poor and uneducated women should be reduced and culturally acceptable alternatives must be considered.

Measuring and managing progress in the establishment of basic health services: the Afghanistan health sector balanced scorecard.

The Ministry of Public Health (MOPH) of Afghanistan has adopted the Balanced Scorecard (BSC) as a tool to measure and manage performance in delivery of a Basic Package of Health Services. Based on results from the 2004 baseline round, the MOPH identified eight of the 29 indicators on the BSC as priority areas for improvement. Like the 2004 round, the 2005 and 2006 BSCs involved a random selection of more than 600 health facilities, 1700 health workers and 5800 patient-provider interactions. The 2005 and 2006 BSCs demonstrated substantial improvements in all eight of the priority areas compared to 2004 baseline levels, with increases in median provincial scores for presence of active village health councils, availability of essential drugs, functional laboratories, provider knowledge, health worker training, use of clinical guidelines, monitoring of tuberculosis treatment, and provision of delivery care. For three of the priority indicators-drug availability, health worker training and provider knowledge-scores remained unchanged or decreased between 2005 and 2006. This highlights the need to ensure that early gains achieved in establishment of health services in Afghanistan are maintained over time. The use of a coherent and balanced monitoring framework to identify priority areas for improvement and measure performance over time reflects an objectives-based approach to management of health services that is proving to be effective in a difficult environment.